| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2001;37:529.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Superoxide Excess in Hypertension and Aging
A Common Cause of Endothelial Dysfunction
From the Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK.
Correspondence to Dr Carlene A. Hamilton, Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, UK. E-mail cah1p{at}clinmed.gla.ac.uk
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
There is evidence in humans that hypertension and aging similarly impair endothelial function, although the mechanism remains unclear. Superoxide anion (O2-) is a major determinant of nitric oxide (NO) bioavailability and thus endothelial function. We sought to determine the relationship between endothelial function, O2-, and age in normotensive Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Aortic rings were removed from female WKY and SHRSP at 3 to 4 months (young) and 9 to 12 months (old). O2- generation by aortic rings was measured before and after removal of the endothelium or incubation with NG nitro-L-arginine methyl ester, diphenyleneiodonium, or apocynin. Levels of p22phox were studied with immunohistochemistry and used as a marker of NAD(P)H oxidase expression. NO bioavailability was significantly lower in old WKY compared with young WKY (P=0.0009) and in old SHRSP compared with young SHRSP (P=0.005). O2- generation was significantly greater in old WKY compared with young WKY (P=0.0001). Removal of the endothelium and NG nitro-L-arginine methyl ester treatment resulted in a significant reduction in O2- generation in old SHRSP (P=0.009 and 0.001, respectively). Diphenyleneiodonium significantly reduced O2- generation in 12-month WKY (P=0.008) and 12-month SHRSP (P=0.009). Apocynin attenuated O2- generation by older WKY (P=0.038) and SHRSP (P=0.028). p22phox was increased in older animals compared with young. We conclude that NO bioavailability decreases with age in female WKY and SHRSP. O2- generation increases with age in WKY and is higher in SHRSP and may contribute to the reduced NO by scavenging. NAD(P)H oxidase may contribute to the age-related increase in O2-.
Key Words: endothelium • nitric oxide • hypertension, experimental • aging
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
There is evidence that in animal models and in humans, impaired endothelial function and a decrease in nitric oxide (NO) bioavailability may occur in hypercholesterolemia,1 2 , diabetes,3 and hypertension4 5 6 despite normal or increased NO production by the endothelium.6 A decrease in NO bioavailability may also occur with aging.7 8 9 10
In a number of animal models of disease, including hypertension11 12 and hypercholesterolemia,13 an increase in superoxide (O2-) occurs concurrent to the decrease in NO bioavailability. O2- rapidly reacts with NO, forming peroxynitrite and decreasing NO bioavailability.14 Thus, it has been proposed that elevations in O2- levels contribute to the impaired endothelial function associated with atherosclerotic disease.13 15
Taddei et al9 proposed that the endothelial dysfunction that occurs in hypertension represents an accelerated form of the dysfunction that occurs with aging. However, the effects of aging on O2- production are less well defined. Huraux and colleagues16 observed a negative correlation between O2- levels and age in human internal mammary arteries. In contrast, Berry et al17 found basal O2- production in human internal mammary arteries to be weakly but positively associated with age.
Potential vascular sources of O2- are endothelial NO synthase (eNOS),18 xanthine oxidase,19 and NAD(P)H oxidase.20 21 eNOS18 and NAD(P)H oxidase22 23 have been proposed to be involved in O2- production in different models of hypertension, whereas xanthine oxidase may be involved in O2- production in hypercholesterolemia.13 eNOS can be inhibited by arginine analogues such as NG nitro-L-arginine methyl ester (L-NAME). NAD(P)H oxidase is composed of at least 5 subunits, and apocynin can inhibit enzymatic activity by preventing association of the subunits. Diphenyleneiodonium (DPI) is a less specific inhibitor of flavin-containing oxidases, including NAD(P)H oxidase.
In this study, the hypothesis that both hypertension and aging result in increased levels of O2- and decreased NO bioavailability in blood vessels from Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) has been examined. The likely source(s) of O2- was also investigated.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Animals
Four groups of female rats were studied: 3- to 4-month-old WKY (n=28), 3- to 4-month-old SHRSP (n=28), 9- to 12-month-old WKY (n=48), and 9- to 12-month-old (n=46) SHRSP. Fewer young animals were used because studies comparing O2- production in young WKY and SHRSP animals had already been undertaken.12 The animals were obtained from the colonies established in Glasgow by brother-and-sister mating, as previously described.24 Blood pressure was measured by tail-cuff plethysmography 1 week before study, according to our published protocol.25 All experiments were approved by the Home Office according to regulations regarding experiments in animals in the United Kingdom.
O2-
Measurement
The animals were given an overdose of barbiturate.
The thoracic aorta and carotid arteries were removed, and
periadventitial tissue was cleaned from the vessels.
O2- was quantified
in 4- to 5-mm segments by lucigenin chemiluminescence, as originally
described by O’Hara et al13
and previously used by our
group.12 17 In
some experiments, the endothelium was removed by
rubbing. In others, either L-NAME (0.1 mmol/L), DPI (0.1
mmol/L), or apocynin (3 mmol/L) was added 60 minutes before
determining O2-
generation. Control rings from the same animal were always assayed in
parallel to each treatment.
O2- generation was
quantified against a standard curve of
O2- generation by
xanthine/xanthine oxidase. Tissue
O2- was expressed
as nanomoles per minute per milligram of wet weight.
Liochev and colleagues26 have reported that high concentrations of lucigenin may produce redox cycling leading to artificial increases in O2-. The concentration of lucigenin used for our initial studies (250 mmol/L) was relatively high; however, we wanted to be able to compare our results with these previously obtained in young animals.12 Studies in which a range of concentrations of lucigenin have been examined report no change17 or lower levels of O2- with lower concentrations of lucigenin but with any differences between experimental groups retained.27
NAD(P)H Oxidase Activity
Aortas and carotids were cleaned of any adhering
connective tissue, rinsed, minced finely with scissors, and
homogenized for 30 seconds with an Ultraturrax T8. The
homogenate was centrifuged for 5 minutes at
1000g and the pellet discarded.
Two milliliters of supernatant was taken for measurement of NAD(P)H
oxidase activity by lucigenin chemiluminescence in the presence of 500
µmol/L NADH or NADPH and 25 µmol/L lucigenin. Protein
concentrations were measured by the method of
Bradford,28 and
O2- generation was
expressed as nanomoles per minute per milligram of
protein.
Organ Bath Studies
Arteries were prepared as for measurement of
O2-, except that
they were cut into 2- to 3-mm rings. The rings were suspended under
1 g tension in individual 10-mL muscle baths containing
physiological saline solution of the following
composition (mmol/L): NaCl 130, KCl 4.7, NaHCO3
14.9, KH2PO4 1.18,
MgSO4 0.7, H2O 1.17,
CaCl2 0.2, H2O 1.6,
glucose 5.5, and CaNa2 EDTA 0.03. The
physiological saline solution was aerated with 95%
O2/5% CO2, and
indomethacin was added to a final bath concentration of
0.1 mmol/L to inhibit any prostanoid-mediated responses. Isometric
tension was measured with Grass force transducers and displayed on a
MacLab.
NO bioavailability was determined as previously described.6 Rings were constricted to their individual EC20 values to phenylephrine (PE). The NOS inhibitor L-NAME was added at a final concentration of 0.1 mmol/L. The increase in the contractile response was taken as a measure of NO bioavailability and expressed as a percentage of the PE EC20.
Immunohistochemistry
Small blocks of thoracic aortas from young and old
rats were embedded in OCT and frozen at -70°C. Sections of 5 µm
were cut, and immunohistochemistry was performed with standard
techniques. Briefly, sections were blocked in 20% horse serum and then
incubated overnight (in a humidified box) at 4°C with a monoclonal
antibody against p22phox kindly supplied by Dr Mark Quinn. For negative
control, the primary antibody was replaced with mouse IgG. Biotinylated
anti-mouse (Vector Labs) at a dilution of 1:200 in 2% horse serum was
incubated for 60 minutes followed by streptavidin conjugated to
horseradish peroxidase. Color was developed by the addition of DAB
(Sigma). The sections were lightly stained in hematoxylin and then
dehydrated through alcohol and xylene. Sections were viewed and scored
by an independent observer unaware of the age or genotype of
the rats. Sections were scored as endothelial or
medial, with 1 representing no staining, 2
representing faint brown, 3 moderate brown, and 4 intense
brown.
Statistics
Vessels from different animals were compared by
2-tailed unpaired t test,
whereas vessels from the same animal with and without treatment were
compared by a paired t test.
Statistical significance was taken as
P<0.05. Results are shown as
mean±SEM, with 95% confidence intervals (CI) where significance was
achieved. Bonferroni correction was applied for analysis of
NADH/NADPH-driven
O2- generation to
allow for multiple
comparisons.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Blood Pressure
The blood pressures (mm Hg±SEM) of the 4 groups of female rats studied were as follows: 3- to 4-month WKY, 117±1; 3- to 4-month SHRSP, 137±4; 9- to 12-month WKY, 115±2; and 9- to 12-month SHRSP, 141±3. Blood pressure was significantly higher in SHRSP than WKY at both ages (P<0.0001): 95% CI for 9- to 12-month WKY versus 9- to 12-month SHRSP, -33.6, -18.7, and for 3- to 4-month WKY versus 3- to 4-month SHRSP, -29.5, -11.8. No age-related effect was noted in either strain.
Basal NO Bioavailability
Addition of L-NAME caused an increase in the
contractile response to PE in all groups studied. However, as shown in
Figure 1a, this increase (% of PE±SEM) was significantly
lower in vessels for 9- to 12-month WKY (296±30, n=11) than for 3- to
4-month WKY (523±51, n=15,
P=0.0009, 95% CI 144, 349) and
in vessels from 9- to 12-month SHRSP (220±28, n=8) than for 3- to
4-month SHRSP (341±26, n=16,
P=0.005; 95% CI, 41,
201).
|
O2-
Levels
O2-
generation in aortas (nmol · min-1 ·
mg-1±SEM) was significantly higher in 9-
to 12-month WKY (2.83±0.30, n=21) compared with 3- to 4-month WKY
(1.06±0.2, n=7, P=0.001; 95%
CI, 1.07, 2.54), but the difference between 9- to 12-month SHRSP
(3.44±0.31 n=23) and 3- to 4-month SHRSP (2.98±0.49 n=9) did not
reach statistical significance
(Figure 1b).
Similar increases in O2- levels with age and hypertension were observed in carotid arteries. O2- values of 0.88±0.18 (n=8) and 3.88±0.50 (n=12) were obtained in vessels from 3- to 4- and 9- to 12-month WKY, respectively (P=0.002; 95% CI, 1.39, 3.55), and 3.35±0.46 (n=12) and 4.89±0.88 (n=12) in 3- to 4- and 9- to 12-month SHRSP (P=0.19). These results are expressed per milligram of wet weight tissue. There was considerable hypertrophy of both carotid arteries and aortas from the older SHRSP, and it is possible that this resulted in an underestimation of O2- levels in these animals.
Sources of
O2- in Aorta From
9- to 12-Month Animals
In older animals, incubation of the aortas with the
NAD(P)H oxidase inhibitor DPI caused a significant decrease
in O2- levels (nmol
· min-1 ·
mg-1±SEM) from 2.13±0.30 to 0.89±0.18
(n=6, P=0.008) in WKY and from
3.04±0.43 to 1.19±0.14 (n=10,
P=0.009; 95% CI, 0.39, 3.09)
in SHRSP
(Figure 2a).
|
As shown in Figure 2b, inhibition of NAD(P)H oxidase activity with apocynin also decreased O2- generation (nmol · min-1 · mg-1±SEM) in older animals, with levels being 1.86±0.25 and 1.06±0.36, respectively, in control and treated vessels from older WKY (n=7, P=0.038; 95% CI, 0.07, 1.78) and 2.29±0.53 and 1.44±0.43, respectively, in control and treated vessels from older SHRSP (n=7, P=0.028; 95% CI, 0.13, 1.57). In addition, apocynin had no significant effect in young WKY, with levels being 1.65±0.41 and 1.65±0.31 in control and treated vessels, respectively, but reduced O2- generation in aortas from young SHRSP from 2.36±0.47 to 1.48±0.27 (n=6, P=0.037; 95% CI, 0.08, 1.77).
The NOS inhibitor L-NAME had no significant effect on O2- generation in 9- to 12-month-old WKY, being 2.58±0.39 and 2.08±0.23 (n=9, P=0.08) in control and treated segments, respectively, but significantly reduced levels in 9- to 12-month-old SHRSP from 2.04±0.44 to 1.55±0.34 (n=6, P=0.02; 95% CI, 0.14, 0.79). Similarly, in WKY, the difference between control (3.42±0.34) and endothelium-denuded vessels (3.01±0.29, n=10) was not significant. In contrast, removal of the endothelium by rubbing decreased O2- levels in SHRSP from 3.63±0.38 to 2.79±0.18 (n=13, P=0.006; 95% CI, 0.30, 1.54).
NADH/NADPH-Driven
O2-
Production
In aortas and carotid arteries, NADH-driven
O2- generation was
greater than NADPH-driven
O2- generation in
all groups. Mean NADH- and NADPH-driven
O2- generation was
higher in older animals
(Table).
This difference was significant for NADH-driven
O2- generation in
carotid arteries from 3- to 4-month versus 9- to 12-month WKY
(P=0.038; 95% CI, 91, 5033)
but failed to reach statistical significance in carotid arteries from
SHRSP or in aorta from either WKY or SHRSP.
|
Immunohistochemistry
Representative sections from young and
old WKY and SHRSP are shown in
Figure 3. Moderate brown staining was evident in the
endothelium of the young vessels in both strains as
1±1 (Figure 3, B and D), whereas the media was scored as 0±1 for
both. In the older WKY rats (Figure 3C), the
endothelium scored 2±1, whereas that of the SHRSP
(Figure 3E) consistently scored 3. Moderate staining, 1±1, was
present in the media of both old WKY and old SHRSP. Because much of
the periadventitial tissue is routinely removed from these vessels, it
was not possible to comment, reliably, on the staining
patterns.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In these studies, we showed that both hypertension and aging result in a decrease in basal NO bioavailability and a corresponding increase in the generation of vascular O2- in female rats. We then went on to investigate the tissue and enzymatic sources of this excess O2-. In the older SHRSP but not WKY, both removal of the endothelium by rubbing and L-NAME treatment caused a significant reduction in O2- levels. Previously, we have made similar observations in young SHRSP,12 and the present results would substantiate our conclusion that eNOS is an important source of O2- in SHRSP.
However, eNOS is not the only the source of O2-. Both DPI and apocynin attenuated O2- production in vessels from SHRSP and older WKY. DPI is frequently used as an inhibitor of NAD(P)H pathways, although it has other actions, including inhibition of NOS.29 The vascular NAD(P)H oxidase consists of at least 5 subunits, with those that make up the membrane-bound cytochrome b558, p22phox, and gp91phox being important for the electron transport and the reduction of molecular oxygen to O2-. Apocynin acts by interfering with NAD(P)H subunit assembly in the membrane and is therefore a more specific inhibitor than DPI.20 Taken together, the inhibition of O2- production by these compounds would be consistent with a role for NAD(P)H oxidase as a source of O2-, particularly in older animals.
Further support for this hypothesis comes from the immunohistochemical studies that showed staining for p22phox in both WKY and SHRSP. Semiquantitatively, this staining was lowest in young WKY and highest in old SHRSP. However, both endothelial and vascular smooth muscle cell expression was upregulated in all the older rats.
As expected for vascular tissue, NADH generated tissue was greater than that generated by NADPH in both aortas and carotid arteries from all groups of animals studied. However, although NADH-generated O2- levels tended to be higher in the older animals, this only reached statistical significance for NADH-driven O2- generation in WKY carotid arteries. The immunohistochemical data suggested that p22phox levels were highest in the endothelium and lowest in vascular smooth muscle. The proportion of vascular smooth muscle was greater in blood vessels from older animals, which is likely to lead to an underestimation of the O2- generation per milligram of protein in the older animals. It is also possible that not all subunits of the NAD(P)H oxidase complex were upregulated to the same extent as p22phox in the older animals.
Although these studies indicate that NAD(P)H oxidase activity increases with age in female rats, these studies do not exclude an additional increase in O2- from other sources in the older animals. For example, although O2- generation from xanthine oxidase is negligible in young WKY and SHRSP, its contribution to O2- generation was not examined in older animals.12
In the studies reported here, a range of techniques was used to substantiate and extend our original findings. Taken together, these studies point to both eNOS and NAD(P)H oxidase as sources of O2- in SHRSP and suggest that the endothelium is an important source of O2- in both young and old SHRSP. In contrast, in young WKY, there is less endothelial involvement in O2- production. O2- generation by NAD(P)H oxidase appears to increase with age, and its primary source appears to be endothelium and adventitia.
All of the studies reported here were carried out in female rats. In contrast to female rats, we have previously observed no decrease in basal nitric oxide bioavailability with age in male WKY or SHRSP.10 Zalba et al22 found no difference in NAD(P)H-driven O2- production in aortas from 16- and 30-week-old male WKY, although an increase was observed in male SHR at 30 weeks. This could suggest that some of the age-related changes reported here are gender-specific. Decreased estrogen levels with age would provide a potential explanation because estrogen has been reported to act as an antioxidant decreasing LDL oxidation and uptake,30 to upregulate eNOS,31 and to decrease vascular O2- production.32 However, decreased estrogen levels are unlikely to be the cause of any of the age-related changes reported here. Most of the older animals used in our study were ex-breeders whose last litter had been weaned <1 month previously. Moreover, plasma estrogen levels do not differ significantly between 3- and 9-month-old animals (unpublished observations).
Conclusions
As with hypertension, the endothelial
dysfunction with aging is due to reduced NO bioavailability as a result
of scavenging by excess vascular
O2-
production. Endothelial NOS contributes
significantly to
O2-
production in hypertensive animals, whereas NAD(P)H oxidase
appears to be an important contributor to age-related increases in
O2-.
|
Acknowledgments |
|---|
This work was supported by the British Heart Foundation Program and Project Grants RG-97009 and PG-200023. The authors thank Emma Jardine for expert technical assistance.
Received October 25, 2000; first decision November 27, 2000; accepted December 11, 2000.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Henry PD, Cabello OA, Chen CH. Hypercholesterolemia and endothelial dysfunction. Curr Opin Lipidol. 1995;6:190–195.[Medline] [Order article via Infotrieve]
2.
Verhaar MC, Wever
RM, Kastelein JJ, van Dam T, Koomans HA, Rabelink TJ.
5-methyltetrahydrofolate, the active form of folic acid, restores
endothelial function in familial
hypercholesterolemia.
Circulation. 1998;97:237–241.
3. Traub O, Van Bibber R. Role of nitric oxide in insulin-dependent diabetes mellitus-related vascular complications. West J Med. 1995;162:439–445.[Medline] [Order article via Infotrieve]
4.
Taddei S, Virdis A,
Mattei P, Salvetti A. Vasodilatation to acetylcholine in primary and
secondary forms of human hypertension.
Hypertension. 1993;21:929–933.
5.
Rees DD, Ben-Ishay
D, Moncada S. Nitric oxide and the regulation of blood pressure in
hypertension-prone and hypertension-resistant Sabra rat.
Hypertension. 1996;28:367–371.
6.
McIntyre M,
Hamilton CA, Rees DD, Reid JL, Dominiczak AF. Sex differences in the
abundance of endothelial nitric oxide in a model of
genetic hypertension.
Hypertension. 1997;30:1517–1524.
7.
Dohi Y, Thiel MA,
Buhler FR, Luscher TF. Activation of endothelial
L-arginine pathway in resistance arteries: effect of age and
hypertension. Hypertension. 1990;16:170–179.
8. Dohi Y, Kojima M, Sato K, Luscher TF. Age-related changes in vascular smooth muscle and endothelium. Drugs Aging. 1995;7:278–291.[Medline] [Order article via Infotrieve]
9.
Taddei S, Virdis A,
Mattei P, Ghiadoni L, Fasolo CB, Sudano I, Salvetti A. Hypertension
causes premature aging of endothelial function in
humans. Hypertension. 1997;29:736–743.
10. McIntyre M, Hamilton CA, Bohr DF, Reid JL, Dominiczak AF. Effects of age and gender on nitric oxide and superoxide in genetic hypertension. Hypertension. 1996;28:705. Abstract.
11.
Bouloumie A,
Bauersachs J, Linz W, Scholkens BA, Wiemer G, Fleming I, Busse R.
Endothelial dysfunction coincides with an enhanced
nitric oxide synthase expression and superoxide anion
production.
Hypertension. 1997;30:934–941.
12.
Kerr S, Brosnan
MJ, McIntyre M, Reid JL, Dominiczak AF, Hamilton CA. Superoxide anion
production is increased in a model of genetic hypertension: the
role of the endothelium.
Hypertension. 1999;33:1353–1358.
13. O’Hara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest. 1993;91:2546–2551.
14.
Rubanyi GM,
Vanhoutte PM. Superoxide anions and hyperoxia inactivate
endothelium-derived relaxing factor.
Am J Physiol Heart Circ
Physiol. 1986;250:H822–H827.
15.
McIntyre M, Bohr
DF, Dominiczak AF. Endothelial function in
hypertension: the role of superoxide anion.
Hypertension. 1999;34:539–545.
16.
Huraux C, Makita
T, Kurz S, Yamaguchi K, Szlam F, Tarpey MM, Wilcox JN, Harrison DG,
Levy JH. Superoxide production, risk factors, and
endothelium-dependent relaxations in human internal
mammary arteries. Circulation. 1999;99:53–59.
17.
Berry C, Hamilton
CA, Brosnan MJ, Magill FG, Berg GA, McMurray JJV, Dominiczak AF.
Investigation into the sources of superoxide in human blood vessels:
angiotensin II increases superoxide production in
human internal mammary arteries.
Circulation. 2000;101:2206–2212.
18. Kerr S, McIntyre M, Brosnan MJ, Reid JL, Hamilton CA, Dominiczak AF. Endothelial generated superoxide contributes to endothelial dysfunction in SHRSP. Hypertension. 1998;32:796. Abstract.
19.
Marczin N,
Antonov A, Papapetropoulos A, Munn DH, Virmani R, Kolodgie FD, Gerrity
R, Catravas JD. Monocyte-induced downregulation of nitric oxide
synthase in cultured aortic endothelial cells.
Arterioscler, Thromb, Vasc
Biol. 1996;16:1095–1103.
20. Meyer JW, Schmitt ME. A central role for the endothelial NADPH oxidase in atherosclerosis. FEBS Lett. 2000;472:1–4.[Medline] [Order article via Infotrieve]
21.
Griendling KK,
Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in
cardiovascular biology and disease.
Circ Res. 2000;86:494–501.
22.
Zalba G, Beaumont
FJ, San Jose G, Fortuno A, Fortuno MA, Etayo JC, Diez J. Vascular
NADH/NADPH oxidase is involved in enhanced superoxide
production in spontaneously hypertensive rats.
Hypertension. 2000;35:1055–1061.
23. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation: contribution to alterations of vasomotor tone. J Clin Invest. 1996;97:1916–1923.[Medline] [Order article via Infotrieve]
24. Dominiczak AF, McLaren Y, Kusel J, Bell D, Goodfriend TL, Bohr DF, Reid JL. Lateral diffusion and fatty acid composition in vascular smooth muscle membrane from stroke-prone spontaneously hypertensive rats. Am J Hypertens. 1993;6:1003–1008.[Medline] [Order article via Infotrieve]
25.
Davidson AO,
Schork N, Jaques BC, Kelman AW, Sutcliffe RG, Reid JL, Dominiczak AF.
Blood pressure in genetically hypertensive rats. Influence of the Y
chromosome. Hypertension. 1995;26:452–459.
26. Liochev SI, Fridovich I. Lucigenin (his-N-methylacridinium) as a mediator of superoxide anion production. Arch Biochem Biophys. 1997;337:115–120.[Medline] [Order article via Infotrieve]
27. Skatchkov MP, Sperling D, Kink U, Mülsch A, Harrison DG, Sindemann I, Meinertz T, Münzel T. Validation of lucigenin as a chemiluminescent probe to monitor vascular superoxide as well as basal vascular nitric oxide production. Biochem Biophys Res Commun. 1999;254:319–324.[Medline] [Order article via Infotrieve]
28. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–254.[Medline] [Order article via Infotrieve]
29. Wang Y, Poon CI, Poon KS, Pang CCY. Inhibitory actions of diphenyleneiodonium on endothelium-dependent vasodilatations in vitro and in vivo. Br J Pharmacol. 1993;110:1232–1238.[Medline] [Order article via Infotrieve]
30.
Hough JL,
Zilversmit DB. Effect of 17 beta estradiol on aortic
cholesterol content and metabolism in
cholesterol-fed rabbits.
Arteriosclerosis. 1986;6:57–63.
31.
Huang A, Sun D,
Koller A, Kaley G. 17ß-Estradiol restores endothelial
nitric oxide release to shear stress in arterioles of male hypertensive
rats. Circulation. 2000;101:94–100.
32.
Barbacanne MA,
Rami J, Michel JB, Souchard JP, Philippe M, Besombes JP, Bayard F,
Arnal JF. Estradiol increases rat aorta
endothelium-derived relaxing factor (EDRF) activity
without changes in endothelial NO synthase gene
expression: possible role of decreased
endothelium-derived superoxide anion
production. Cardiovasc
Res. 1999;41:672–681.
This article has been cited by other articles:
 |
|
 |
|
  X. Zhou, H. G. Bohlen, J. L. Unthank, and S. J. Miller Abnormal nitric oxide production in aged rat mesenteric arteries is mediated by NAD(P)H oxidase-derived peroxide Am J Physiol Heart Circ Physiol, December 1, 2009; 297(6): H2227 - H2233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Copp, L. F. Ferreira, K. F. Herspring, D. M. Hirai, B. S. Snyder, D. C. Poole, and T. I. Musch The effects of antioxidants on microvascular oxygenation and blood flow in skeletal muscle of young rats Exp Physiol, September 1, 2009; 94(9): 961 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Graham, N. N. Huynh, C. A. Hamilton, E. Beattie, R. A.J. Smith, H. M. Cocheme, M. P. Murphy, and A. F. Dominiczak Mitochondria-Targeted Antioxidant MitoQ10 Improves Endothelial Function and Attenuates Cardiac Hypertrophy Hypertension, August 1, 2009; 54(2): 322 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Collins, C. J. Lyon, X. Xia, J. Z. Liu, R. K. Tangirala, F. Yin, R. Boyadjian, A. Bikineyeva, D. Pratico, D. G. Harrison, et al. Age-Accelerated Atherosclerosis Correlates With Failure to Upregulate Antioxidant Genes Circ. Res., March 27, 2009; 104(6): e42 - e54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Lesniewski, M. L. Connell, J. R. Durrant, B. J. Folian, M. C. Anderson, A. J. Donato, and D. R. Seals B6D2F1 Mice Are a Suitable Model of Oxidative Stress-Mediated Impaired Endothelium-Dependent Dilation With Aging J Gerontol A Biol Sci Med Sci, February 10, 2009; (2009) gln049v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. Herspring, L. F. Ferreira, S. W. Copp, B. S. Snyder, D. C. Poole, and T. I. Musch Effects of antioxidants on contracting spinotrapezius muscle microvascular oxygenation and blood flow in aged rats J Appl Physiol, December 1, 2008; 105(6): 1889 - 1896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Seals, C. A. DeSouza, A. J. Donato, and H. Tanaka Habitual exercise and arterial aging J Appl Physiol, October 1, 2008; 105(4): 1323 - 1332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Csiszar, M. Wang, E. G. Lakatta, and Z. Ungvari Inflammation and endothelial dysfunction during aging: role of NF-{kappa}B J Appl Physiol, October 1, 2008; 105(4): 1333 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Donato, I. Eskurza, K. L. Jablonski, L. B. Gano, G. L. Pierce, and D. R. Seals Cytochrome P-450 2C9 signaling does not contribute to age-associated vascular endothelial dysfunction in humans J Appl Physiol, October 1, 2008; 105(4): 1359 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lopez-Ruiz, J. Sartori-Valinotti, L. L. Yanes, R. Iliescu, and J. F. Reckelhoff Sex differences in control of blood pressure: role of oxidative stress in hypertension in females Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H466 - H474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, A. R. Sapuri-Butti, H. H. Aung, A. N. Parikh, and J. C. Rutledge Triglyceride-rich lipoprotein lipolysis increases aggregation of endothelial cell membrane microdomains and produces reactive oxygen species Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H237 - H244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. N. Das Risk of type 2 diabetes mellitus in those with hypertension Eur. Heart J., April 1, 2008; 29(7): 952 - 953. [Full Text] [PDF]
|
|
|
|
|
|
H. Bulckaen, G. Prevost, E. Boulanger, G. Robitaille, V. Roquet, C. Gaxatte, G. Garcon, B. Corman, P. Gosset, P. Shirali, et al. Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1562 - H1570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Guazzi, M. Samaja, R. Arena, M. Vicenzi, and M. D. Guazzi Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure J. Am. Coll. Cardiol., November 27, 2007; 50(22): 2136 - 2144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Brown, S. P. Didion, J. J. Andresen, and F. M. Faraci Effect of Aging, MnSOD Deficiency, and Genetic Background on Endothelial Function: Evidence for MnSOD Haploinsufficiency Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 1941 - 1946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jacobson, C. Yan, Q. Gao, T. Rincon-Skinner, A. Rivera, J. Edwards, A. Huang, G. Kaley, and D. Sun Aging enhances pressure-induced arterial superoxide formation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1344 - H1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Csiszar, N. Labinskyy, Z. Orosz, Z. Xiangmin, R. Buffenstein, and Z. Ungvari Vascular aging in the longest-living rodent, the naked mole rat Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H919 - H927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ungvari, Z. Orosz, N. Labinskyy, A. Rivera, Z. Xiangmin, K. Smith, and A. Csiszar Increased mitochondrial H2O2 production promotes endothelial NF-{kappa}B activation in aged rat arteries Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H37 - H47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, L. Wang, C.-W. Lee, T. A. Dawson, and D. J. Paterson Noradrenergic Cell Specific Gene Transfer With Neuronal Nitric Oxide Synthase Reduces Cardiac Sympathetic Neurotransmission in Hypertensive Rats Hypertension, July 1, 2007; 50(1): 69 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Donato, I. Eskurza, A. E. Silver, A. S. Levy, G. L. Pierce, P. E. Gates, and D. R. Seals Direct Evidence of Endothelial Oxidative Stress With Aging in Humans: Relation to Impaired Endothelium-Dependent Dilation and Upregulation of Nuclear Factor-{kappa}B Circ. Res., June 8, 2007; 100(11): 1659 - 1666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Miller, L. E. Norton, M. P. Murphy, M. C. Dalsing, and J. L. Unthank The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2523 - H2531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. G. Schrage, J. H. Eisenach, and M. J. Joyner Ageing reduces nitric-oxide- and prostaglandin-mediated vasodilatation in exercising humans J. Physiol., February 15, 2007; 579(1): 227 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Heaton, D. Li, S. C. Almond, T. A. Dawson, L. Wang, K. M. Channon, and D. J. Paterson Gene Transfer of Neuronal Nitric Oxide Synthase into Intracardiac Ganglia Reverses Vagal Impairment in Hypertensive Rats Hypertension, February 1, 2007; 49(2): 380 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, J. S. Beckman, and L. Liaudet Nitric Oxide and Peroxynitrite in Health and Disease Physiol Rev, January 1, 2007; 87(1): 315 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Csiszar, N. Labinskyy, K. Smith, A. Rivera, Z. Orosz, and Z. Ungvari Vasculoprotective Effects of Anti-Tumor Necrosis Factor-{alpha} Treatment in Aging Am. J. Pathol., January 1, 2007; 170(1): 388 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Labinskyy, A. Csiszar, Z. Orosz, K. Smith, A. Rivera, R. Buffenstein, and Z. Ungvari Comparison of endothelial function, O2-{middle dot} and H2O2 production, and vascular oxidative stress resistance between the longest-living rodent, the naked mole rat, and mice. Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2698 - H2704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Guazzi, M. Berti, S. Belletti, G. Reina, and M. D. Guazzi Exercise metaboreflex activation and endothelial function impairment in atrial fibrillation Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2396 - H2402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Feletou and P. M. Vanhoutte Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture) Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H985 - H1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Heaton, M. Lei, D. Li, S. Golding, T. A. Dawson, R. M. Mohan, and D. J. Paterson Remodeling of the Cardiac Pacemaker L-Type Calcium Current and Its {beta}-Adrenergic Responsiveness in Hypertension After Neuronal NO Synthase Gene Transfer Hypertension, September 1, 2006; 48(3): 443 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Brown, Y. Chu, D. D. Lund, D. D. Heistad, and F. M. Faraci Gene transfer of extracellular superoxide dismutase protects against vascular dysfunction with aging Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2600 - H2605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Eskurza, Z. D. Kahn, and D. R. Seals Xanthine oxidase does not contribute to impaired peripheral conduit artery endothelium-dependent dilatation with ageing J. Physiol., March 15, 2006; 571(3): 661 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Fang, H. Sun, D. M. Arrick, and W. G. Mayhan Inhibition of NADPH oxidase improves impaired reactivity of pial arterioles during chronic exposure to nicotine J Appl Physiol, February 1, 2006; 100(2): 631 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sun, H. Zheng, E. Molacek, Q. Fang, K. P. Patel, and W. G. Mayhan Role of NAD(P)H Oxidase in Alcohol-Induced Impairment of Endothelial Nitric Oxide Synthase-Dependent Dilation of Cerebral Arterioles Stroke, February 1, 2006; 37(2): 495 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Wilcox Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension? Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R913 - R935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Najjar, A. Scuteri, and E. G. Lakatta Arterial Aging: Is It an Immutable Cardiovascular Risk Factor? Hypertension, September 1, 2005; 46(3): 454 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Brandes, I. Fleming, and R. Busse Endothelial aging Cardiovasc Res, May 1, 2005; 66(2): 286 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Becker, A. Adler, A. Schneeberger, H. Huang, Z. Wang, E. Walsh, A. Koller, and T. H. Hintze Hyperhomocysteinemia, a Cardiac Metabolic Disease: Role of Nitric Oxide and the p22phox Subunit of NADPH Oxidase Circulation, April 26, 2005; 111(16): 2112 - 2118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sugita, M. Fujimoto, T. Yasukawa, N. Shimizu, M. Sugita, S. Yasuhara, J. A. J. Martyn, and M. Kaneki Inducible Nitric-oxide Synthase and NO Donor Induce Insulin Receptor Substrate-1 Degradation in Skeletal Muscle Cells J. Biol. Chem., April 8, 2005; 280(14): 14203 - 14211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Arikan and S. Sen Endothelial Damage and Hemostatic Markers in Patients with Uncomplicated Mild-to-Moderate Hypertension and Relationship with Risk Factors Clinical and Applied Thrombosis/Hemostasis, April 1, 2005; 11(2): 147 - 159. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Barton Ageing as a determinant of renal and vascular disease: role of endothelial factors Nephrol. Dial. Transplant., March 1, 2005; 20(3): 485 - 490. [Full Text] [PDF]
|
|
|
|
|
|
C. Bell, J. M. Carson, N. W. Motte, and D. R. Seals Ascorbic acid does not affect the age-associated reduction in maximal cardiac output and oxygen consumption in healthy adults J Appl Physiol, March 1, 2005; 98(3): 845 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Reckelhoff Sex Steroids, Cardiovascular Disease, and Hypertension: Unanswered Questions and Some Speculations Hypertension, February 1, 2005; 45(2): 170 - 174. [Full Text] [PDF]
|
|
|
|
|
|
P. Francia, C. delli Gatti, M. Bachschmid, I. Martin-Padura, C. Savoia, E. Migliaccio, P. G. Pelicci, M. Schiavoni, T. F. Luscher, M. Volpe, et al. Deletion of p66shc Gene Protects Against Age-Related Endothelial Dysfunction Circulation, November 2, 2004; 110(18): 2889 - 2895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Sullivan, E. D. Loomis, M. Collins, J. D. Imig, E. W. Inscho, and J. S. Pollock Age-related alterations in NOS and oxidative stress in mesenteric arteries from male and female rats J Appl Physiol, October 1, 2004; 97(4): 1268 - 1274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Delles, M. P. Schneider, S. Oehmer, I. Fleischmann, E. F. Fleischmann, and R. E. Schmieder Increased response of renal perfusion to the antioxidant vitamin C in type 2 diabetes Nephrol. Dial. Transplant., October 1, 2004; 19(10): 2513 - 2518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Spinetti, M. Wang, R. Monticone, J. Zhang, D. Zhao, and E. G. Lakatta Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1397 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ungvari, A. Csiszar, P. M. Kaminski, M. S. Wolin, and A. Koller Chronic High Pressure-Induced Arterial Oxidative Stress: Involvement of Protein Kinase C-Dependent NAD(P)H Oxidase and Local Renin-Angiotensin System Am. J. Pathol., July 1, 2004; 165(1): 219 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Monahan, I. Eskurza, and D. R. Seals Ascorbic acid increases cardiovagal baroreflex sensitivity in healthy older men Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2113 - H2117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sun, A. Huang, E. H. Yan, Z. Wu, C. Yan, P. M. Kaminski, T. D. Oury, M. S. Wolin, and G. Kaley Reduced release of nitric oxide to shear stress in mesenteric arteries of aged rats Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2249 - H2256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Haendeler, J. Hoffmann, J. F. Diehl, M. Vasa, I. Spyridopoulos, A. M. Zeiher, and S. Dimmeler Antioxidants Inhibit Nuclear Export of Telomerase Reverse Transcriptase and Delay Replicative Senescence of Endothelial Cells Circ. Res., April 2, 2004; 94(6): 768 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Eskurza, K. D. Monahan, J. A. Robinson, and D. R. Seals Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing J. Physiol., April 1, 2004; 556(1): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Kaminker Is Akt the Mastermind Behind Age-Related Heart Disease? Sci. Aging Knowl. Environ., February 25, 2004; 2004(8): pe8 - 8. [Abstract] [Full Text]
|
|
|
|
|
|
H. Xu, G. D. Fink, and J. J. Galligan Tempol Lowers Blood Pressure and Sympathetic Nerve Activity But Not Vascular O2- in DOCA-Salt Rats Hypertension, February 1, 2004; 43(2): 329 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Adler, H. Huang, M. S. Wolin, and P. M. Kaminski Oxidant Stress Leads to Impaired Regulation of Renal Cortical Oxygen Consumption by Nitric Oxide in the Aging Kidney J. Am. Soc. Nephrol., January 1, 2004; 15(1): 52 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ju, D. J. Behm, S. Nerurkar, M. E. Eybye, R. E. Haimbach, A. R. Olzinski, S. A. Douglas, and R. N. Willette p38 MAPK Inhibitors Ameliorate Target Organ Damage in Hypertension: Part 1. p38 MAPK-Dependent Endothelial Dysfunction and Hypertension J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 932 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Woodman, E. M. Price, and M. H. Laughlin Selected Contribution: Aging impairs nitric oxide and prostacyclin mediation of endothelium-dependent dilation in soleus feed arteries J Appl Physiol, November 1, 2003; 95(5): 2164 - 2170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Bivalacqua, M. F. Usta, H. C. Champion, P. J. Kadowitz, and W. J. G. Hellstrom Endothelial Dysfunction in Erectile Dysfunction: Role of the Endothelium in Erectile Physiology and Disease J Androl, November 1, 2003; 24(6_suppl): S17 - S37. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bell, P. P. Jones, and D. R. Seals Oxidative Stress Does Not Modulate Metabolic Rate or Skeletal Muscle Sympathetic Activity with Primary Aging in Adult Humans J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4950 - 4954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Solhaug Pathophysiological role for oxidative stress in geriatric vascular dysfunction Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R524 - R525. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Payne, J. F. Reckelhoff, and R. A. Khalil Role of oxidative stress in age-related reduction of NO-cGMP-mediated vascular relaxation in SHR Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R542 - R551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lassegue and R. E. Clempus Vascular NAD(P)H oxidases: specific features, expression, and regulation Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R277 - R297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Higashi, S. Sasaki, K. Nakagawa, M. Kimura, K. Noma, S. Sasaki, K. Hara, H. Matsuura, C. Goto, T. Oshima, et al. Low body mass index is a risk factor forimpaired endothelium-dependent vasodilation in humans: role of nitric oxide and oxidative stress J. Am. Coll. Cardiol., July 16, 2003; 42(2): 256 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Bivalacqua, J. S. Armstrong, J. Biggerstaff, A. B. Abdel-Mageed, P. J. Kadowitz, W. J. G. Hellstrom, and H. C. Champion Gene transfer of extracellular SOD to the penis reduces O Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1408 - H1421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. McBride, F. J. Carr, D. Graham, N. H. Anderson, J. S. Clark, W. K. Lee, F. J. Charchar, M. J. Brosnan, and A. F. Dominiczak Microarray Analysis of Rat Chromosome 2 Congenic Strains Hypertension, March 1, 2003; 41(3): 847 - 853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. X. Zhang, A.-P. Zou, and P.-L. Li Ceramide-induced activation of NADPH oxidase and endothelial dysfunction in small coronary arteries Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H605 - H612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Piech, C. Dessy, X. Havaux, O. Feron, and J.-L. Balligand Differential regulation of nitric oxide synthases and their allosteric regulators in heart and vessels of hypertensive rats Cardiovasc Res, February 1, 2003; 57(2): 456 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Hamilton, M. J. Brosnan, S. Al-Benna, G. Berg, and A. F. Dominiczak NAD(P)H Oxidase Inhibition Improves Endothelial Function in Rat and Human Blood Vessels Hypertension, November 1, 2002; 40(5): 755 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mukai, H. Shimokawa, M. Higashi, K. Morikawa, T. Matoba, J. Hiroki, I. Kunihiro, H. M.A. Talukder, and A. Takeshita Inhibition of Renin-Angiotensin System Ameliorates Endothelial Dysfunction Associated With Aging in Rats Arterioscler Thromb Vasc Biol, September 1, 2002; 22(9): 1445 - 1450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Csiszar, Z. Ungvari, J. G. Edwards, P. Kaminski, M. S. Wolin, A. Koller, and G. Kaley Aging-Induced Phenotypic Changes and Oxidative Stress Impair Coronary Arteriolar Function Circ. Res., June 14, 2002; 90(11): 1159 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Orallo, E. Alvarez, M. Camina, J. M. Leiro, E. Gomez, and P. Fernandez The Possible Implication of trans-Resveratrol in the Cardioprotective Effects of Long-Term Moderate Wine Consumption Mol. Pharmacol., February 1, 2002; 61(2): 294 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.M. Vanhoutte Ageing and endothelial dysfunction Eur. Heart J. Suppl., February 1, 2002; 4(suppl_A): A8 - A17. [Abstract] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
Z. Bagi, Z. Ungvari, and A. Koller Xanthine Oxidase-Derived Reactive Oxygen Species Convert Flow-Induced Arteriolar Dilation to Constriction in Hyperhomocysteinemia: Possible Role of Peroxynitrite Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 28 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Attia, A. M. G. Verhagen, E. S. G. Stroes, E. E. van Faassen, H.-J. Grone, S. J. De Kimpe, H. A. Koomans, B. Braam, and J. A. Joles Vitamin E Alleviates Renal Injury, but Not Hypertension, during Chronic Nitric Oxide Synthase Inhibition in Rats J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2585 - 2593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. Wassmann, U. Laufs, D. Stamenkovic, W. Linz, J.-P. Stasch, K. Ahlbory, R. Rosen, M. Bohm, and G. Nickenig Raloxifene Improves Endothelial Dysfunction in Hypertension by Reduced Oxidative Stress and Enhanced Nitric Oxide Production Circulation, April 30, 2002; 105(17): 2083 - 2091. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||