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(Hypertension. 1995;25:1083-1089.)
© 1995 American Heart Association, Inc.
Articles |
In Vivo Evidence for Microvascular Oxidative Stress in Spontaneously Hypertensive Rats
Hydroethidine Microfluorography
From the Institute for Biomedical Engineering, University of California at San Diego, La Jolla.
Correspondence to Dr Geert W. Schmid-Schönbein, Institute for Biomedical Engineering and Department of Bioengineering, University of California at San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0412.
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Abstract |
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Abstract The factors that predispose to the accelerated organ injury that accompanies the hypertensive syndrome have remained speculative and without a firm experimental basis. Indirect evidence has suggested that a key feature may be related to an enhanced oxygen radical production. The purpose of this study was to refine and use a technique to visualize evidence of spontaneous microvascular oxidative stress in vivo in the spontaneously hypertensive rat (SHR) compared with its normotensive control, the Wistar-Kyoto rat (WKY). We investigated the effects of adrenal glucocorticoids on the microvascular oxidative stress sequence. The mesentery was superfused with hydroethidine, a reduced, nonfluorescent precursor of ethidium bromide. In the presence of oxidative challenge, hydroethidine is transformed intracellularly into the fluorescent compound ethidium bromide, which binds to DNA and can be detected by virtue of its red fluorescence. The fluorescent light emission from freshly exteriorized and otherwise unstimulated mesentery microvessels was recorded by digital microscopy. The number of ethidium bromide–positive nuclei along the arteriolar and venular walls in SHR was found to be significantly increased above the level exhibited by WKY. The elevation in ethidium bromide fluorescence in SHR arterioles could be attenuated by a synthetic glucocorticoid inhibitor and in rats subjected to adrenalectomy. The administration of glucocorticoids after adrenalectomy by injection of dexamethasone restored the oxidative reaction in SHR arterioles. Treatment with dimethylthiourea and with a xanthine oxidase inhibitor attenuated the superoxide formation. Although a nitric oxide synthase inhibitor (NG-nitro-L-arginine methyl ester) enhanced the ethidium bromide staining in WKY, it did not affect that in SHR. Our findings suggest an enhancement of spontaneous oxidative stress in the microvascular wall of SHR that appears to be associated with glucocorticoid synthesis.
Key Words: free radicals • arterioles • adrenalectomy • glucocorticoids
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Introduction |
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Recently, we obtained direct evidence that oxygen radicals are produced spontaneously from activated circulating leukocytes of spontaneously hypertensive rats (SHR) but not in their normotensive control, the Wistar-Kyoto rat (WKY).1 Our analysis of the SHR model of hypertension has shown that key aspects of the syndrome might be associated with glucocorticoid pathways.2 It was demonstrated that the increase in the number of activated circulating leukocytes in SHR could be overridden by treatment with a synthetic glucocorticoid inhibitor (RU486)3 as well as by bilateral adrenalectomy.4 These observations led us to entertain the question of whether other cells in the cardiovascular system, such as endothelium, might also be involved in spontaneous oxygen radical production and whether the overproduction of oxygen radicals could be related to the action of steroid hormones.
Hydroethidine, the sodium borohydride–reduced derivative of ethidium bromide (EB),5 6 which permeates the cell membranes easily, is an oxygen radical–sensitive fluorescent probe. The intracellular hydroethidine can be directly oxidized to form red fluorescent EB, which in turn is trapped in the nucleus by intercalation into DNA.7 Hydroethidine is especially sensitive to superoxide anion and to a lesser degree to hydrogen peroxide. The end product EB emits light at a longer wavelength (590 nm), with comparatively little light contamination of the signal from the background fluorescence in the tissue.
We designed the present series of studies to investigate the occurrence of spontaneous mesenteric microvascular oxidative stress in SHR compared with WKY with the use of digital microfluorography to determine the presence of EB formation. The involvement of adrenal glucocorticoid in spontaneous oxidative stress and its correlation to arteriolar tone were explored.
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Methods |
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Animal Preparation
All animal procedures were previously reviewed and approved by the University of California at San Diego Animal Subject Committee. SHR (n=33) and WKY (n=32) (Charles River Breeding Laboratories, Wilmington, Mass) were used at 13 to 14 weeks of age. A cohort of SHR (n=10) and WKY (n=9) was subjected to bilateral adrenalectomy at 12 weeks.4 These bilaterally adrenalectomized SHR and WKY were fed standard rat chow with 0.9% (wt/vol) NaCl in their drinking water ad libitum and were maintained in a light-controlled holding facility for 1 week.4 Control SHR and WKY were fed standard rat chow and water ad libitum. The rats appeared alert and without overt signs of infection or weight loss. Completeness of the surgical adrenalectomy was ascertained by postmortem examination of the suprarenal region.
After general anesthesia with pentobarbital sodium (40 mg/kg IM), a femoral catheter (PE-50, Clay-Adams) was inserted and mean arterial pressure measured. Rats were placed on a heating pad and covered with a blanket maintained at 37°C. The abdomen was opened by a small midline incision. The ileocecal portion of the mesentery was gently exteriorized and draped over a plastic support for intravital microscopy, as described previously.8 The preparation was kept at 37°C and continuously superfused (1.0 mL/min) with a Krebs-Henseleit bicarbonate-buffered solution saturated with 95% N2/5% CO2. Special precautions were taken to avoid interruption of the suffusion solution on the tissue because even superficial drying causes rapid cell injury.
To provide further support that the difference in EB stain between SHR and WKY was not related to differences in strain, we investigated the microvascular oxidation of hydroethidine in normotensive Sprague-Dawley rats.
Intravital Fluorescence Microscopy
The mesenteric microcirculation was visualized through an
intravital microscope (x55 water immersion objective lens, Leitz) with
the use of a digital color charge coupled device (CCD) camera (DEI-470,
Optronics Engineering). Single unbranched arterioles in the field with
a diameter between 20 and 30 µm and approximately 150 µm in length
and venules with a diameter between 30 and 40 µm and approximately
150 µm in length were selected for study. Arterioles are easily
identified by their position in the microvascular network (at the
inflows), the existence of vascular smooth muscle, and divergent
bifurcations. At the level at which arterioles were tested in our
experiments, they exhibited very little leukocyte margination. Vessels
were classified as venules on the basis of their position in the
convergent part of the network with at least two to three convergent
capillary channels. A digital gain-control mode in the color CCD camera
allowed suitable transmission images to be obtained. The camera
sensitivity and shutter speed were set at constant values (contrast=0,
brightness=0, manual integration=
) so that the camera served
as a light intensity indicator. To elicit fluorescent images, we
illuminated the preparation with a 200-W mercury lamp. The light was
passed through a quartz collector, heat filter (model KG-2, Zeiss), and
excitation filter (490 nm, Leitz) for epi-illumination. Fluorescence
emission from the specimen was passed through a band-pass filter (590
nm) and onto the CCD camera.
Photobleaching of the fluorescent images was avoided by keeping the light exposure time of the tissue limited to less than 1 second by means of a shutter between the light source and a filter cube. Transillumination images were also recorded immediately after the fluorescence images. During the intervening periods, the shutter for the excitation light was kept closed. The images were recorded with a videocassette recorder (model AG-127OP, Panasonic) for playback analysis. Fluorescence images of the microvessels were transferred into an image digitizer (512x512, 8-bit deep, Image 1.53 with a Macintosh IIci laboratory computer) and stored on a retractable hard disk for subsequent analysis at a fixed camera control setting on the digital CCD camera controller. The number of EB-positive nuclei along arterioles or venules (NEB) was counted every 15 minutes for 120 minutes. At the end of the experiments, the tissue was superfused with absolute ethanol for 10 minutes followed by EB superfusion to specify the total number of the nuclei lining the vessel wall (NT). The EB-positive number of nuclei was computed as (NEB/NT)x100 (%).
Vessel diameters were measured off-line with a videoimage-shearing monitor (model 907, IPM). The diameters reported in the study refer to inner lumen measurements; no corrections were made for noncircular cross sections.9 In addition to steady-state values, each microvessel was studied after local application of a vasodilator (1.0 mg/mL papaverine in normal saline). This dose was sufficient to eliminate active tone in the arterioles, because only vessel dilation, not narrowing at constant pressure, was observed in the presence of papaverine. Measurements before and after application of papaverine provided steady-state lumen diameters (dss) and maximal diameters (dmax), respectively. All diameter measurements were made at constant central blood pressures native to each animal. The tone (T) was computed as T=(dmax-dss)/dmax and is a nondimensional parameter that specified the degree of active smooth muscle constriction, such that T=0% in dilated vessels and T=100% in fully constricted vessels and vessels with an occluded lumen.10
Hydroethidine Superfusion
After an initial 20-minute stabilization period, the mesenteric
preparation was superfused with the perfusate, and a background
autofluorescence image in the selected tissue area was recorded and
stored in the memory of a laboratory computer (Macintosh Computer IIci,
Apple Computer Co, assisted by IMAGE 1.53 software,
National Institute of Health public domain software). The preparation
was then superfused with a buffer solution containing hydroethidine
(5.0 µmol/L, Polyscience, Inc) for 120 minutes. The number of
EB-stained nuclei was counted per unit length of microvessel. The
selection of microvessels was limited to arterioles and venules.
Interventions
To modify the extent of glucocorticoid involvement, we
administered RU486 (33.3 mg/kg body wt IM mifepristone, Roussel-Uclaf),
a synthetic glucocorticoid inhibitor, 6 hours before the microvascular
experiments. Intramuscular injection of RU486 has a significant effect
on the systemic leukocyte count in SHR.3 To explore the
effect of glucocorticoid restoration in adrenalectomized rats on EB
fluorescence, we injected dexamethasone 21-acetate (Sigma Chemical Co)
at a dose of 0.5 mg/kg body wt per day IM for 5 days in a separate set
of rats.
In additional experiments, to verify the role of oxygen radical
formation in the mesenteric vascular wall, we pretreated the mesentery
with dimethylthiourea (2 mmol/L in superfusate, Aldrich
Chemical Co), which decomposes the hydroxyl radical and hydrogen
peroxide.11 To explore the value of xanthine
oxidase–mediated superoxide formation, we also pretreated the
mesentery with
(-)-8-(3-methoxy-4-phenylsulfinyl-phenyl)pyrazolo(1,5-
)-1,3,5-triazine-4-olate
monohydrate [(-)BOF 4272, Otsuka Pharmaceutical Co, 10 nmol/L in
superfusate], which is a synthetic xanthine oxidase inhibitor, as well
as its negative control reagent,
(+)-8-(3-methoxy-4-phenylsulfinyl-phenyl)pyrazolo(1,5-)-1,3,5-triazine-4-olate
monohydrate [(+)BOF 4272)]. (-)BOF 4272 at 10 nmol/L attenuated more
than 60% of superoxide production in an in vitro cell-free reaction
mixture containing hypoxanthine and xanthine oxidase but did not
attenuate phorbol ester–induced superoxide release by isolated
neutrophils, suggesting that this reagent does not have a direct
scavenging effect on superoxide anions.12
To investigate the role of nitric oxide (NO) for the oxidation of hydroethidine, an NO synthase inhibitor, we superfused NG-nitro-L-arginine methyl ester (L-NAME, 50 µmol/L) for 20 minutes before the onset of hydroethidine superfusion and continued it for the entire experimental period.
Statistical Analysis
Statistical comparison of EB-stained nuclear number (percent)
among groups was determined by one-way layout ANOVA and
Scheffé-type multiple comparison test. All values are reported as
mean±SD. A value of P<.05 was considered statistically
significant.
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Results |
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During continuous superfusion of hydroethidine, no significant changes in microvascular velocity as well as in leukocyte–endothelial cell adhesive interaction were observed.
EB fluorescence was strikingly enhanced in the wall of SHR arterioles compared with WKY arterioles without application of a stimulator (Fig 1a). The elevated level of EB fluorescence in SHR arterioles (Fig 1b) was attenuated by surgical adrenalectomy (Fig 1c).
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A similar enhancement of EB fluorescence was seen in mesenteric venules of SHR compared with those of WKY. Again, no additional stimulation of the microcirculation was required (Fig 2). In contrast to the arterioles, the elevated EB fluorescence in SHR venules (Fig 2b) was not significantly attenuated after adrenalectomy (Fig 2c).
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The majority of EB-stained nuclei in arterioles and venules had a longitudinally oriented spindle shape and were positioned on the inner lining of the vascular wall, suggesting that they were endothelial cells.
Fig 3a depicts the time course for the relative number of EB-positive nuclei (percent) along the mesenteric arteriolar wall. The number was significantly greater in SHR mesentery compared with WKY mesentery. The number of EB-positive nuclei along mesenteric venules was also significantly higher in SHR (Fig 3b). In both strains, the increase in the number of EB-positive nuclei was significantly greater in arteriolar walls compared with venular walls.
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The enhanced number of EB-positive nuclei (percent) along mesenteric arterioles 60 minutes after the onset of hydroethidine superfusion in SHR was blunted by adrenalectomy or by treatment with a glucocorticoid inhibitor (RU486) but was restored by glucocorticoid supplementation with dexamethasone (Fig 4a). In contrast, in WKY the number was lower and there was no significant difference among groups.
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P<.05 compared with SHR control;
**P<.05 compared with adrenalectomized SHR.The number of EB-positive nuclei (percent) along mesenteric venules 60 minutes after the onset of hydroethidine superfusion was significantly increased in SHR compared with WKY. All groups had low values of EB-positive nuclei, and there were no significant differences between groups (Fig 4b).
The enhanced oxidation of hydroethidine along mesenteric arterioles at 60 minutes was significantly attenuated by dimethylthiourea or (-)BOF 4272 treatment (Fig 5a). L-NAME superfusion did not elicit a significant increase in EB-positive nuclei in SHR over the number seen in untreated, control SHR (Fig 5a). L-NAME superfusion induced a significant increase in EB-positive nuclei in WKY to the level observed in untreated, control SHR (Fig 5a).
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The enhanced number of EB-positive nuclei (percent) along mesenteric venules in SHR 60 minutes after the onset of hydroethidine superfusion could be attenuated by treatment with dimethylthiourea or (-)BOF 4272 (Fig 5b). In WKY venules, all groups except the L-NAME group had low values of EB-positive nuclei, and there were no significant differences between groups (Fig 5b). L-NAME superfusion induced a significant increase in EB-positive nuclei in WKY to the level observed in untreated, control SHR (Fig 5b).
There was a positive correlation between arteriolar tone and the local EB-positive nuclei (percent) for the different groups (Fig 6). Arteriolar tone in SHR was significantly higher than in WKY (P<.05). There was a significant linear correlation between the relative EB-positive nuclei and arteriolar tone at 60 minutes after the onset of hydroethidine superfusion in SHR, WKY, and adrenalectomized WKY.
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): n=8, y=0.31x-3.11,
r=.92; adrenalectomized WKY (
): n=5,
y=0.20x+4.21, r=.83; spontaneously
hypertensive rats (SHR, 
): n=8,
y=0.14x+6.61, r=.74; adrenalectomized
SHR (
): n=6, y=0.19x+8.87,
r=.59.In mesenteric arterioles or venules of normotensive Sprague-Dawley rats, no statistically significant differences compared with WKY could be demonstrated in the number of EB-positive nuclei 60 minutes after the onset of hydroethidine superfusion (arteriole, 32.7±12.0%; venule, 18.8±3.8%).
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Discussion |
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The present microfluorographic studies provide the first in vivo demonstration of oxidative stress in a hypertensive animal model without any additional stimulation. Quantitative estimates of the extent of EB staining as a consequence of oxidative stress were obtained by recording the number of EB-positive nuclei per unit length of a vessel. On this basis, the staining in the arterioles was greater than in venules and greater in SHR for both types of microvessels.
The agent hydroethidine may serve as a tool for detecting spontaneous oxidative changes in a microcirculation under several other in vivo conditions. Hydroethidine has been used in the past as a measure of the oxidative burst in neutrophils7 that results from activation of the membrane-bound NADPH oxidase via an electron transfer reaction. The superoxide anion produced is then dismutated to H2O2 either spontaneously or via superoxide dismutase. The hydroethidine moiety, which is the sodium borohydride–reduced product of EB, was initially developed as a vital dye that could cross cell membranes and label DNA.5 13 The resulting visual assessment of the EB staining in a cell after oxidation of hydroethidine is thus primarily a measure of nuclear fluorescence.14 Earlier studies on phagocytic cells have demonstrated that EB fluorescence reflected the generation of superoxide anion O2- and that O2- was acting to oxidize the hydroethidine to EB.7 Carter et al14 reported that superoxide anion resulted in a 10-fold increase in fluorescence intensity of EB compared with other oxidizing agents. According to their cell-free assay,14 when the relative intensity of EB fluorescence with potassium superoxide (KO2, equivalent to 200 µmol/L O2-) was defined as 100%, the intensities with 200 µmol/L H2O2 and with 200 µmol/L H2O2 plus 200 U/mL horseradish peroxidase were 7.8% and 10.43%, respectively.
We have previously used a method for demonstrating in vivo H2O2 levels directly with a fluorescence precursor, 2',7'-dichlorofluorescein (DCFH) diacetate8 or 5-(6)-carboxy-2',7'-dichlorofluorescin (CDCFH) diacetate.15 In the present study we elected to rely on hydroethidine microfluorography as a measure of the oxidative stress in microvessels for the following reason: hydroethidine is more superoxide sensitive. DCFH and CDCFH methods depend on intracellular esterase activity; therefore, it has been difficult to compare groups of cells that have different levels of esterase activity. Furthermore, inasmuch as DCFH and CDCFH fluorescence is emitted by the same range of wavelengths as the background autofluorescence characteristic of collagen fibers, it was difficult to make a comparison in a situation that may also be accompanied by a change in tissue structure involving collagen fibers. Another problem with esterase-dependent fluorescent probes was their leakage after damage of the cell membrane. Although DCFH and CDCFH allow quantification of the oxidative stress in tissue, all-or-none determination of oxidative stress with hydroethidine is well suited for the purpose of the present study.
The demonstration that the arteriolar wall in the SHR microcirculation is a site of oxygen free radical production may be relevant to a number of the different abnormalities observed in the hypertensive strain. The release of H2O2 was found to activate intercellular adhesion molecule-116 and major histocompatibility complex-1 expression in human umbilical vein endothelial cells.17 It has also been proposed that such high levels of oxygen radicals may also underlie the elevated arteriolar tone that has been documented in the SHR.10
Dimethylthiourea is a small, permeable, and relatively nontoxic scavenger of H2O2 and the H2O2-derived product hydroxyl radical.11 In the present study, dimethylthiourea significantly attenuated the microvascular EB staining in SHR, even in the arterioles of WKY, suggesting that oxygen radicals could be spontaneously produced along the arteriolar wall and that their extent was enhanced in SHR. In view of the fact that a xanthine oxidase inhibitor, (-)BOF 4272, significantly attenuated the elevated oxidative changes in SHR mesentery, the possibility exists that an overproduction of oxygen radicals might be generated at least in part by way of the xanthine–xanthine oxidase system. The fact that significant attenuation of hydroethidine oxidation occurred by specific inhibition of a xanthine oxidase, which is predominantly located in endothelial cells,18 and the shape and position of EB-stained nuclei along the innermost cell layer in microvessels suggest that hydroethidine oxidation occurred mainly in endothelial cells.
Glucocorticoid blockade by RU486, as well as by bilateral adrenalectomy, serves to attenuate EB staining in arterioles and also modify vascular responses under identical conditions. In a recent report, we were able to show that the dilator response of the mesenteric arterioles (the maximal change in tone) after histamine superfusion was blunted in SHR and that such a blunted response could be circumvented by bilateral adrenalectomy (H.S. et al, unpublished data, 1994). Pretreatment with dexamethasone significantly counteracted this mesenteric arteriolar dilator response in the adrenalectomized SHR (H.S. et al, unpublished data, 1994). The present study directly supports a strong correlation between local EB fluorescence and arteriolar tone (Fig 6).
Our data demonstrate that the degree of EB staining is considerably higher along the arteriolar wall than along the venular wall. Such a distinctive difference could possibly be ascribed to the heterogeneity of the mechanisms leading to the production of oxygen radical species. Since the transformation of hydroethidine is in large part a result of O2- and H2O2 formation, the arteriolar wall, which is exposed to higher levels of oxygen than the venular walls, would be more avidly stained by EB. However, the fact that venular levels were also elevated in SHR indicates that some mechanism other than high oxygen content and the high blood pressure seen in arterioles may determine the levels of superoxide formation in SHR.
The evolution of the hypertension syndrome has been assumed to involve a glucocorticoid pathway in an important way.19 The present evidence demonstrates that a synthetic glucocorticoid inhibitor, as well as bilateral adrenalectomy, can significantly diminish the elevated levels of EB staining in the arteriolar wall of SHR mesentery. The experimental elevation of glucocorticoid levels by injection after adrenalectomy restored this visual index of oxidative stress, suggesting a possible involvement of adrenal glucocorticoids in the observed oxidative change along the microvascular wall of SHR. Glucocorticoids are potent inhibitors of the induction of a calcium-independent (inducible) NO synthase.20 21 A number of studies indicate that the flow-induced dilation of arterioles mediated by NO is impaired in SHR.22 Thus, there may be in SHR an impairment of the shear stress stimulation of NO synthesis in response to a shift in shear stress22 through activation of a potassium channel that has been shown to be coupled to a pertussis toxin–sensitive G protein.23 Our current data support the concept that endogenous NO release from microvascular endothelium may minimize spontaneous oxidative stress by inactivating O2-.15 The present data on L-NAME–treated WKY are consistent with the previous data in Wistar rats,15 which showed that L-NAME superfusion induced leukocyte-independent and leukocyte-dependent oxidative stress in arterioles and venules. The fact that L-NAME effects on EB staining in SHR arterioles and venules were not significantly different from those in the untreated groups would suggest that NO activity is suppressed in SHR. One of the possibilities in this respect is that elevated levels of endogenous glucocorticoids in SHR evoke an overexpression of oxygen radicals in microvascular endothelium by suppressing inducible NO synthase. It has also been reported that glucocorticoids decrease prostaglandin formation in endothelial cells24 by way of an induced biosynthesis of lipocortin25 so as to inhibit phospholipase A2 activity. Superoxide might also be generated from prostaglandin H synthase during the conversion from prostaglandin G2 to prostaglandin H2 in the presence of NADH or NADPH.26 27
Glucocorticoids are known to enhance catecholamine-stimulated inotropism,28 modulate ß-adrenergic receptor density,29 and regulate the ability of ß-adrenergic receptors to form a high-affinity state.30 In addition, glucocorticoids enhance vascular reactivity to norepinephrine.31 Adrenergic modification along these various lines by a glucocorticoid may also serve as one of the modulating factors leading to a higher level of EB staining in SHR. Such reciprocal effects of glucocorticoids and adrenergic components can contribute to a significant suppression of oxidative stress in SHR after adrenalectomy.
In conclusion, microfluorography with the use of hydroethidine suggests an enhanced formation of oxygen radicals in the wall of the SHR microvasculature. Ancillary experiments further suggest that such oxidative changes in hypertensives may be related to the elevated levels of adrenal glucocorticoids in SHR.
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Acknowledgments |
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This work was completed during the tenure of a research fellowship for Dr H. Suzuki from the American Heart Association, California Affiliate. This work was supported by National Institutes of Health grant HL-10881. We thank Prof D.T. O'Connor, Veterans Administration Medical Center, La Jolla, Calif, for providing RU486 and Otsuka Pharmaceutical Factory, Inc, Naruto, Japan, for providing (-)BOF 4272 and (+)BOF 4272.
Received October 28, 1994; first decision November 21, 1994; accepted January 20, 1995.
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  E. Belaidi, M. Joyeux-Faure, C. Ribuot, S. H. Launois, P. Levy, and D. Godin-Ribuot Major role for hypoxia inducible factor-1 and the endothelin system in promoting myocardial infarction and hypertension in an animal model of obstructive sleep apnea. J. Am. Coll. Cardiol., April 14, 2009; 53(15): 1309 - 1317. [Abstract] [Full Text] [PDF]
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 N. Baudry, E. Laemmel, and E. Vicaut In vivo reactive oxygen species production induced by ischemia in muscle arterioles of mice: involvement of xanthine oxidase and mitochondria Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H821 - H828. [Abstract] [Full Text] [PDF]
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 S. M. Arribas, C. J. Daly, M. C. Gonzalez, and J. C. McGrath Imaging the vascular wall using confocal microscopy J. Physiol., October 1, 2007; 584(1): 5 - 9. [Abstract] [Full Text] [PDF]
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 K. Tsukimori, H. Nakano, and N. Wake Difference in Neutrophil Superoxide Generation During Pregnancy Between Preeclampsia and Essential Hypertension Hypertension, June 1, 2007; 49(6): 1436 - 1441. [Abstract] [Full Text] [PDF]
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 T. R. Nurkiewicz and M. A. Boegehold High salt intake reduces endothelium-dependent dilation of mouse arterioles via superoxide anion generated from nitric oxide synthase Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1550 - R1556. [Abstract] [Full Text] [PDF]
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A. A. Banday, A. B. Muhammad, F. R. Fazili, and M. Lokhandwala Mechanisms of Oxidative Stress-Induced Increase in Salt Sensitivity and Development of Hypertension in Sprague-Dawley Rats Hypertension, March 1, 2007; 49(3): 664 - 671. [Abstract] [Full Text] [PDF]
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 G. L. Baumbach, S. P. Didion, and F. M. Faraci Hypertrophy of Cerebral Arterioles in Mice Deficient in Expression of the Gene for CuZn Superoxide Dismutase Stroke, July 1, 2006; 37(7): 1850 - 1855. [Abstract] [Full Text] [PDF]
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 C. S. Packer Soluble guanylate cyclase (sGC) down-regulation by abnormal extracellular matrix proteins as a novel mechanism in vascular dysfunction: Implications in metabolic syndrome Cardiovasc Res, February 1, 2006; 69(2): 302 - 303. [Full Text] [PDF]
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N. E. Taylor and A. W. Cowley Jr. Effect of renal medullary H2O2 on salt-induced hypertension and renal injury Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1573 - R1579. [Abstract] [Full Text] [PDF]
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 L. T. de Richelieu, C. M. Sorensen, N.-H. Holstein-Rathlou, and M. Salomonsson NO-independent mechanism mediates tempol-induced renal vasodilation in SHR Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1227 - F1234. [Abstract] [Full Text] [PDF]
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 R. Vera, M. Galisteo, I. C. Villar, M. Sanchez, A. Zarzuelo, F. Perez-Vizcaino, and J. Duarte Soy Isoflavones Improve Endothelial Function in Spontaneously Hypertensive Rats in an Estrogen-Independent Manner: Role of Nitric-Oxide Synthase, Superoxide, and Cyclooxygenase Metabolites J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1300 - 1309. [Abstract] [Full Text] [PDF]
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T. Berg Increased counteracting effect of eNOS and nNOS on an {alpha}1-adrenergic rise in total peripheral vascular resistance in spontaneous hypertensive rats Cardiovasc Res, September 1, 2005; 67(4): 736 - 744. [Abstract] [Full Text] [PDF]
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 H. Zhao, J. Joseph, H. M. Fales, E. A. Sokoloski, R. L. Levine, J. Vasquez-Vivar, and B. Kalyanaraman Detection and characterization of the product of hydroethidine and intracellular superoxide by HPLC and limitations of fluorescence PNAS, April 19, 2005; 102(16): 5727 - 5732. [Abstract] [Full Text] [PDF]
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L. Yanes, D. Romero, R. Iliescu, V. E. Cucchiarelli, L. A. Fortepiani, F. Santacruz, W. Bell, H. Zhang, and J. F. Reckelhoff Systemic arterial pressure response to two weeks of Tempol therapy in SHR: involvement of NO, the RAS, and oxidative stress Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2005; 288(4): R903 - R908. [Abstract] [Full Text] [PDF]
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I. Drenjancevic-Peric and J. H. Lombard Reduced Angiotensin II and Oxidative Stress Contribute to Impaired Vasodilation in Dahl Salt-Sensitive Rats on Low-Salt Diet Hypertension, April 1, 2005; 45(4): 687 - 691. [Abstract] [Full Text] [PDF]
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F. A. DeLano, R. Balete, and G. W. Schmid-Schonbein Control of oxidative stress in microcirculation of spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H805 - H812. [Abstract] [Full Text] [PDF]
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S. A. Phillips, F. A. Sylvester, and J. C. Frisbee Oxidant stress and constrictor reactivity impair cerebral artery dilation in obese Zucker rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R522 - R530. [Abstract] [Full Text] [PDF]
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S. C. Schafer, T. Wallerath, E. I. Closs, C. Schmidt, P. M. Schwarz, U. Forstermann, and H.-A. Lehr Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H436 - H444. [Abstract] [Full Text] [PDF]
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 K. Sato, T. Komaru, H. Shioiri, S. Takeda, K. Takahashi, H. Kanatsuka, M. Nakayama, and K. Shirato Hypercholesterolemia Impairs Transduction of Vasodilator Signals Derived From Ischemic Myocardium: Myocardium-Microvessel Cross-Talk Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 2034 - 2039. [Abstract] [Full Text] [PDF]
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S. Sela, R. Mazor, M. Amsalam, C. Yagil, Y. Yagil, and B. Kristal Primed Polymorphonuclear Leukocytes, Oxidative Stress, and Inflammation Antecede Hypertension in the Sabra Rat Hypertension, November 1, 2004; 44(5): 764 - 769. [Abstract] [Full Text] [PDF]
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L. Park, J. Anrather, P. Zhou, K. Frys, G. Wang, and C. Iadecola Exogenous NADPH Increases Cerebral Blood Flow Through NADPH Oxidase-Dependent and -Independent Mechanisms Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1860 - 1865. [Abstract] [Full Text] [PDF]
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M. d. C. P. Franco, Z. B. Fortes, E. H. Akamine, E. M. Kawamoto, C. Scavone, L. R. G. de Britto, M. N. Muscara, S. A. Teixeira, R. C. A. Tostes, M. H. C. Carvalho, et al. Tetrahydrobiopterin improves endothelial dysfunction and vascular oxidative stress in microvessels of intrauterine undernourished rats J. Physiol., July 1, 2004; 558(1): 239 - 248. [Abstract] [Full Text] [PDF]
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R. S. Fries, P. Mahboubi, N. R. Mahapatra, S. K. Mahata, N. J. Schork, G. W. Schmid-Schoenbein, and D. T. O'Connor Neuroendocrine Transcriptome in Genetic Hypertension: Multiple Changes in Diverse Adrenal Physiological Systems Hypertension, June 1, 2004; 43(6): 1301 - 1311. [Abstract] [Full Text] [PDF]
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 T. Kishi, Y. Hirooka, Y. Kimura, K. Ito, H. Shimokawa, and A. Takeshita Increased Reactive Oxygen Species in Rostral Ventrolateral Medulla Contribute to Neural Mechanisms of Hypertension in Stroke-Prone Spontaneously Hypertensive Rats Circulation, May 18, 2004; 109(19): 2357 - 2362. [Abstract] [Full Text] [PDF]
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M. M. Tarpey, D. A. Wink, and M. B. Grisham Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2004; 286(3): R431 - R444. [Abstract] [Full Text] [PDF]
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J. Zhu, T. Mori, T. Huang, and J. H. Lombard Effect of high-salt diet on NO release and superoxide production in rat aorta Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H575 - H583. [Abstract] [Full Text] [PDF]
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 S. CUZZOCREA, E. MAZZON, L. DUGO, R. DI PAOLA, A. P. CAPUTI, and D. SALVEMINI Superoxide: a key player in hypertension FASEB J, January 1, 2004; 18(1): 94 - 101. [Abstract] [Full Text] [PDF]
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Y.-F. Chen, A. W. Cowley Jr., and A.-P. Zou Increased H2O2 counteracts the vasodilator and natriuretic effects of superoxide dismutation by tempol in renal medulla Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2003; 285(4): R827 - R833. [Abstract] [Full Text] [PDF]
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A. D. Dobrian, S. D. Schriver, T. Lynch, and R. L. Prewitt Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity Am J Physiol Renal Physiol, October 1, 2003; 285(4): F619 - F628. [Abstract] [Full Text] [PDF]
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G. E. Callera, R. M. Touyz, S. A. Teixeira, M. N. Muscara, M. H. C. Carvalho, Z. B. Fortes, D. Nigro, E. L. Schiffrin, and R. C. Tostes ETA Receptor Blockade Decreases Vascular Superoxide Generation in DOCA-Salt Hypertension Hypertension, October 1, 2003; 42(4): 811 - 817. [Abstract] [Full Text] [PDF]
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M. d. C. P Franco, E. H. Akamine, G. S. Di Marco, D. E. Casarini, Z. B Fortes, R. C.A Tostes, M. H. C Carvalho, and D. Nigro NADPH oxidase and enhanced superoxide generation in intrauterine undernourished rats: involvement of the renin-angiotensin system Cardiovasc Res, September 1, 2003; 59(3): 767 - 775. [Abstract] [Full Text] [PDF]
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A. Makino, M. M. Skelton, A.-P. Zou, and A. W. Cowley Jr Increased Renal Medullary H2O2 Leads to Hypertension Hypertension, July 1, 2003; 42(1): 25 - 30. [Abstract] [Full Text] [PDF]
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S. Meng, G. W. Cason, A. W. Gannon, L. C. Racusen, and R. D. Manning Jr Oxidative Stress in Dahl Salt-Sensitive Hypertension Hypertension, June 1, 2003; 41(6): 1346 - 1352. [Abstract] [Full Text] [PDF]
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 Y. Chu, S. Iida, D. D. Lund, R. M. Weiss, G. F. DiBona, Y. Watanabe, F. M. Faraci, and D. D. Heistad Gene Transfer of Extracellular Superoxide Dismutase Reduces Arterial Pressure in Spontaneously Hypertensive Rats: Role of Heparin-Binding Domain Circ. Res., March 7, 2003; 92(4): 461 - 468. [Abstract] [Full Text] [PDF]
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K. M. Hoagland, K. G. Maier, and R. J. Roman Contributions of 20-HETE to the Antihypertensive Effects of Tempol in Dahl Salt-Sensitive Rats Hypertension, March 1, 2003; 41(3): 697 - 702. [Abstract] [Full Text] [PDF]
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T. Iuchi, M. Akaike, T. Mitsui, Y. Ohshima, Y. Shintani, H. Azuma, and T. Matsumoto Glucocorticoid Excess Induces Superoxide Production in Vascular Endothelial Cells and Elicits Vascular Endothelial Dysfunction Circ. Res., January 10, 2003; 92(1): 81 - 87. [Abstract] [Full Text] [PDF]
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J. C. Frisbee, K. G. Maier, and D. W. Stepp Oxidant stress-induced increase in myogenic activation of skeletal muscle resistance arteries in obese Zucker rats Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2160 - H2168. [Abstract] [Full Text] [PDF]
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N. J. Schork, J. P. Gardner, L. Zhang, D. Fallin, B. Thiel, H. Jakubowski, and A. Aviv Genomic Association/Linkage of Sodium Lithium Countertransport in CEPH Pedigrees Hypertension, November 1, 2002; 40(5): 619 - 628. [Abstract] [Full Text] [PDF]
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S. P. Didion, M. J. Ryan, G. L. Baumbach, C. D. Sigmund, and F. M. Faraci Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1569 - H1576. [Abstract] [Full Text] [PDF]
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S. Meng, L. J. Roberts II, G. W. Cason, T. S. Curry, and R. D. Manning Jr. Superoxide dismutase and oxidative stress in Dahl salt-sensitive and -resistant rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2002; 283(3): R732 - R738. [Abstract] [Full Text] [PDF]
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M. A.W. Broeders, G. J. Tangelder, D. W. Slaaf, R. S. Reneman, and M. G.A. oude Egbrink Hypercholesterolemia Enhances Thromboembolism in Arterioles but Not Venules: Complete Reversal by L-Arginine Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 680 - 685. [Abstract] [Full Text] [PDF]
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 M. Rathaus and J. Bernheim Oxygen species in the microvascular environment: regulation of vascular tone and the development of hypertension Nephrol. Dial. Transplant., February 1, 2002; 17(2): 216 - 221. [Abstract] [Full Text] [PDF]
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D. M. Lenda and M. A. Boegehold Effect of a high-salt diet on oxidant enzyme activity in skeletal muscle microcirculation Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H395 - H402. [Abstract] [Full Text] [PDF]
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A. E. Midaoui and J. de Champlain Prevention of Hypertension, Insulin Resistance, and Oxidative Stress by {alpha}-Lipoic Acid Hypertension, February 1, 2002; 39(2): 303 - 307. [Abstract] [Full Text] [PDF]
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A. P. V. Dantas, R. C.A. Tostes, Z. B. Fortes, S. G. Costa, D. Nigro, and M. H. C. Carvalho In Vivo Evidence for Antioxidant Potential of Estrogen in Microvessels of Female Spontaneously Hypertensive Rats Hypertension, February 1, 2002; 39(2): 405 - 411. [Abstract] [Full Text] [PDF]
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A. Makino, M. M. Skelton, A.-P. Zou, R. J. Roman, and A. W. Cowley Jr Increased Renal Medullary Oxidative Stress Produces Hypertension Hypertension, February 1, 2002; 39(2): 667 - 672. [Abstract] [Full Text] [PDF]
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 D. Nyhan, S. Kim, S. Dunbar, D. Li, A. Shoukas, and D. E. Berkowitz Impaired pulmonary artery contractile responses in a rat model of microgravity: role of nitric oxide J Appl Physiol, January 1, 2002; 92(1): 33 - 40. [Abstract] [Full Text] [PDF]
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G. Zalba, G. S. Jose, M. U. Moreno, M. A. Fortuno, A. Fortuno, F. J. Beaumont, and J. Diez Oxidative Stress in Arterial Hypertension: Role of NAD(P)H Oxidase Hypertension, December 1, 2001; 38(6): 1395 - 1399. [Abstract] [Full Text] [PDF]
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M.-G. Feng, S. A. W. Dukacz, and R. L. Kline Selective effect of tempol on renal medullary hemodynamics in spontaneously hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2001; 281(5): R1420 - R1425. [Abstract] [Full Text] [PDF]
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J. C. Frisbee Impaired dilation of skeletal muscle microvessels to reduced oxygen tension in diabetic obese Zucker rats Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1568 - H1574. [Abstract] [Full Text] [PDF]
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J. C. Frisbee and D. W. Stepp Impaired NO-dependent dilation of skeletal muscle arterioles in hypertensive diabetic obese Zucker rats Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1304 - H1311. [Abstract] [Full Text] [PDF]
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A. D. Dobrian, S. D. Schriver, and R. L. Prewitt Role of Angiotensin II and Free Radicals in Blood Pressure Regulation in a Rat Model of Renal Hypertension Hypertension, September 1, 2001; 38(3): 361 - 366. [Abstract] [Full Text] [PDF]
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G. Zalba, G. S. Jose, F. J. Beaumont, M. A. Fortuno, A. Fortuno, and J. Diez Polymorphisms and Promoter Overactivity of the p22phox Gene in Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats Circ. Res., February 2, 2001; 88(2): 217 - 222. [Abstract] [Full Text] [PDF]
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L. O. Lerman, K. A. Nath, M. Rodriguez-Porcel, J. D. Krier, R. S. Schwartz, C. Napoli, and J. C. Romero Increased Oxidative Stress in Experimental Renovascular Hypertension Hypertension, February 1, 2001; 37(2): 541 - 546. [Abstract] [Full Text] [PDF]
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A.-P. Zou, N. Li, and A. W. Cowley Jr. Production and Actions of Superoxide in the Renal Medulla Hypertension, February 1, 2001; 37(2): 547 - 553. [Abstract] [Full Text] [PDF]
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A. D. Dobrian, M. J. Davies, S. D. Schriver, T. J. Lauterio, and R. L. Prewitt Oxidative Stress in a Rat Model of Obesity-Induced Hypertension Hypertension, February 1, 2001; 37(2): 554 - 560. [Abstract] [Full Text] [PDF]
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M. A. W. Broeders, G.-J. Tangelder, D. W. Slaaf, R. S. Reneman, and M. G. A. o. Egbrink Endogenous Nitric Oxide and Prostaglandins Synergistically Counteract Thromboembolism in Arterioles but Not in Venules Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 163 - 169. [Abstract] [Full Text] [PDF]
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N. D. Vaziri, Z. Ni, F. Oveisi, and D. L. Trnavsky-Hobbs Effect of Antioxidant Therapy on Blood Pressure and NO Synthase Expression in Hypertensive Rats Hypertension, December 1, 2000; 36(6): 957 - 964. [Abstract] [Full Text] [PDF]
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H. Cai and D. G. Harrison Endothelial Dysfunction in Cardiovascular Diseases: The Role of Oxidant Stress Circ. Res., November 10, 2000; 87(10): 840 - 844. [Abstract] [Full Text] [PDF]
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I. Hernandez, J. L. Delgado, J. Diaz, T. Quesada, M. J. G. Teruel, M. C. Llanos, and L. F. Carbonell 17beta -Estradiol prevents oxidative stress and decreases blood pressure in ovariectomized rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2000; 279(5): R1599 - R1605. [Abstract] [Full Text] [PDF]
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F. Lacy, M. T. Kailasam, D. T. O'Connor, G. W. Schmid-Schonbein, and R. J. Parmer Plasma Hydrogen Peroxide Production in Human Essential Hypertension : Role of Heredity, Gender, and Ethnicity Hypertension, November 1, 2000; 36(5): 878 - 884. [Abstract] [Full Text] [PDF]
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G. Zalba, F. J. Beaumont, G. S. Jose, A. Fortuno, M. A. Fortuno, J. C. Etayo, and J. Diez Vascular NADH/NADPH Oxidase Is Involved in Enhanced Superoxide Production in Spontaneously Hypertensive Rats Hypertension, May 1, 2000; 35(5): 1055 - 1061. [Abstract] [Full Text] [PDF]
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 U. P. Kodavanti, M. C. Jackson, A. D. Ledbetter, B. C. Starcher, P. A. Evansky, A. Harewood, D. W. Winsett, and D. L. Costa The Combination of Elastase and Sulfur Dioxide Exposure Causes COPD-Like Lesions in the Rat Chest, May 1, 2000; 117(5_suppl_1): 299S - 302S. [Full Text] [PDF]
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A. Huang, D. Sun, and A. Koller Shear Stress-Induced Release of Prostaglandin H2 in Arterioles of Hypertensive Rats Hypertension, April 1, 2000; 35(4): 925 - 930. [Abstract] [Full Text] [PDF]
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A. D. Dobrian, M. J. Davies, R. L. Prewitt, and T. J. Lauterio Development of Hypertension in a Rat Model of Diet-Induced Obesity Hypertension, April 1, 2000; 35(4): 1009 - 1015. [Abstract] [Full Text] [PDF]
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K. K. Griendling, D. Sorescu, and M. Ushio-Fukai NAD(P)H Oxidase : Role in Cardiovascular Biology and Disease Circ. Res., March 17, 2000; 86(5): 494 - 501. [Abstract] [Full Text] [PDF]
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M. Usui, K. Egashira, S. Kitamoto, M. Koyanagi, M. Katoh, C. Kataoka, H. Shimokawa, and A. Takeshita Pathogenic Role of Oxidative Stress in Vascular Angiotensin-Converting Enzyme Activation in Long-Term Blockade of Nitric Oxide Synthesis in Rats Hypertension, October 1, 1999; 34(4): 546 - 551. [Abstract] [Full Text] [PDF]
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H. Suzuki, F. A. Delano, N. Jamshidi, D. Katz, M. Mori, K. Kosaki, R. A. Gottlieb, H. Ishii, and G. W. Schmid-Schonbein Enhanced DNA fragmentation in the thymus of spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H2135 - H2140. [Abstract] [Full Text] [PDF]
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J. R. Kersten and D. C. Warltier Modulation of the adaptive response to myocardial ischemia by coexisting disease Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H2268 - H2270. [Full Text] [PDF]
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C. G. Schnackenberg and C. S. Wilcox Two-Week Administration of Tempol Attenuates Both Hypertension and Renal Excretion of 8-Iso Prostaglandin F2{alpha} Hypertension, January 1, 1999; 33(1): 424 - 428. [Abstract] [Full Text] [PDF]
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T. Marumo, V. B. Schini-Kerth, R. P. Brandes, and R. Busse Glucocorticoids Inhibit Superoxide Anion Production and p22 Phox mRNA Expression in Human Aortic Smooth Muscle Cells Hypertension, December 1, 1998; 32(6): 1083 - 1088. [Abstract] [Full Text] [PDF]
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A. Huang, D. Sun, G. Kaley, and A. Koller Superoxide Released to High Intra-arteriolar Pressure Reduces Nitric Oxide–Mediated Shear Stress– and Agonist-Induced Dilations Circ. Res., November 2, 1998; 83(9): 960 - 965. [Abstract] [Full Text] [PDF]
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J. Laakso, E. Mervaala, J.-J. Himberg, T.-L. Teravainen, H. Karppanen, H. Vapaatalo, and R. Lapatto Increased Kidney Xanthine Oxidoreductase Activity in Salt-Induced Experimental Hypertension Hypertension, November 1, 1998; 32(5): 902 - 906. [Abstract] [Full Text] [PDF]
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C. G. Schnackenberg, W. J. Welch, and C. S. Wilcox Normalization of Blood Pressure and Renal Vascular Resistance in SHR With a Membrane-Permeable Superoxide Dismutase Mimetic : Role of Nitric Oxide Hypertension, July 1, 1998; 32(1): 59 - 64. [Abstract] [Full Text] [PDF]
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F. J. Miller, D. D. Gutterman, C. D. Rios, D. D. Heistad, and B. L. Davidson Superoxide Production in Vascular Smooth Muscle Contributes to Oxidative Stress and Impaired Relaxation in Atherosclerosis Circ. Res., June 29, 1998; 82(12): 1298 - 1305. [Abstract] [Full Text] [PDF]
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P. S. Tsao, J. Niebauer, R. Buitrago, P. S. Lin, B.-y. Wang, J. P. Cooke, Y-d. Ida Chen, and G. M. Reaven Interaction of Diabetes and Hypertension on Determinants of Endothelial Adhesiveness Arterioscler. Thromb. Vasc. Biol., June 1, 1998; 18(6): 947 - 953. [Abstract] [Full Text] [PDF]
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H. Suzuki, F. A. DeLano, D. A. Parks, N. Jamshidi, D. N. Granger, H. Ishii, M. Suematsu, B. W. Zweifach, and G. W. Schmid-Schonbein Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats PNAS, April 14, 1998; 95(8): 4754 - 4759. [Abstract] [Full Text] [PDF]
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T.-C. Chou, M.-H. Yen, C.-Y. Li, and Y.-A. Ding Alterations of Nitric Oxide Synthase Expression With Aging and Hypertension in Rats Hypertension, February 1, 1998; 31(2): 643 - 648. [Abstract] [Full Text] [PDF]
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M. A. W. Broeders, G.-J. Tangelder, D. W. Slaaf, R. S. Reneman, and M. G. A. oude Egbrink Endogenous Nitric Oxide Protects Against Thromboembolism in Venules But Not in Arterioles Arterioscler. Thromb. Vasc. Biol., January 1, 1998; 18(1): 139 - 145. [Abstract] [Full Text] [PDF]
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A. Swei, F. Lacy, F. A. DeLano, and G. W. Schmid-Schonbein Oxidative Stress in the Dahl Hypertensive Rat Hypertension, December 1, 1997; 30(6): 1628 - 1633. [Abstract] [Full Text]
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A. Huang and A. Koller Endothelin and Prostaglandin H2 Enhance Arteriolar Myogenic Tone in Hypertension Hypertension, November 1, 1997; 30(5): 1210 - 1215. [Abstract] [Full Text]
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H. Suzuki, B. W. Zweifach, and G. W. Schmid-Schonbein Vasodilator Response of Mesenteric Arterioles to Histamine in Spontaneously Hypertensive Rats Hypertension, September 1, 1995; 26(3): 397 - 400. [Abstract] [Full Text]
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B. Rodriguez-Iturbe, Y. Quiroz, M. Nava, L. Bonet, M. Chavez, J. Herrera-Acosta, R. J. Johnson, and H. A. Pons Reduction of renal immune cell infiltration results in blood pressure control in genetically hypertensive rats Am J Physiol Renal Physiol, February 1, 2002; 282(2): F191 - F201. [Abstract] [Full Text] [PDF]
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M. A.W. Broeders, G. J. Tangelder, D. W. Slaaf, R. S. Reneman, and M. G.A. oude Egbrink Hypercholesterolemia Enhances Thromboembolism in Arterioles but Not Venules: Complete Reversal by L-Arginine Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 680 - 685. [Abstract] [Full Text] [PDF]
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