Donate Help Contact The AHA Sign In Home
American Heart Association
Hypertension
Search: search_blue_button Advanced Search
Hypertension. 2000;36:957-964

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vaziri, N. D.
Right arrow Articles by Trnavsky-Hobbs, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vaziri, N. D.
Right arrow Articles by Trnavsky-Hobbs, D. L.
Related Collections
Right arrow Biochemistry and metabolism
Right arrow Other hypertension
Right arrow Hypertension - basic studies
Right arrow Coagulation and fibronolysis
Right arrow Genetics of cardiovascular disease
Right arrow Oxidant stress
Right arrow Endothelium/vascular type/nitric oxide

(Hypertension. 2000;36:957.)
© 2000 American Heart Association, Inc.


Scientific Contributions

Effect of Antioxidant Therapy on Blood Pressure and NO Synthase Expression in Hypertensive Rats

Nosratola D. Vaziri; Zhenmin Ni; Fariba Oveisi; Debra L. Trnavsky-Hobbs

From the Division of Nephrology, Department of Medicine, University of California, Irvine.


*    Abstract
up arrowTop
*Abstract
down arrowIntroduction
down arrowMethods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Abstract—Earlier studies have demonstrated evidence for increased reactive oxygen species, enhanced NO synthase (NOS) expression, and elevated NO production in spontaneously hypertensive rats (SHR). Given the negative-feedback regulation of NOS by NO, we hypothesized that enhanced NO inactivation by ROS may contribute to compensatory upregulation of NOS in SHR. The present study was designed to test this hypothesis. Eight-week-old male SHR and Wistar-Kyoto rats were treated for 3 weeks with either a placebo or the potent antioxidant, lazaroid (desmethyltirilazad, 10 mg · kg-1 · d-1, by gastric gavage). Tail arterial blood pressure, urinary excretion of NO metabolites (ie, nitrate and nitrite), and immunodetectable NOS isotype proteins in the vascular, renal, cardiac, and cerebral tissues were measured. The placebo-treated SHR group showed a marked elevation of blood pressure and a significant upregulation of aorta, kidney, and cardiac tissue endothelial and inducible NOS (eNOS and iNOS, respectively) proteins and of brain and renal tissue neuronal NOS. Lazaroid therapy ameliorated hypertension and mitigated the upregulation of eNOS and iNOS in vascular, renal, and cardiac tissues but had limited effect on the expression of renal and brain neuronal NOS. In contrast, lazaroid therapy had no effect on blood pressure, urinary nitrate and nitrite excretion, or tissue NOS isotype expressions in the Wistar-Kyoto group. These findings support the role of oxidative stress in the genesis and/or maintenance of hypertension and compensatory upregulation of the expression of eNOS and iNOS in SHR.


Key Words: stress • free radicals • hypertension, experimental • antioxidants • nitric oxide • nitric oxide synthase


*    Introduction
up arrowTop
up arrowAbstract
*Introduction
down arrowMethods
down arrowResults
down arrowDiscussion
down arrowReferences
 
We have recently demonstrated a marked upregulation of renal and vascular expressions of endothelial and inducible NO synthase (eNOS and iNOS, respectively) proteins in young spontaneously hypertensive rats (SHR).1 These observations substantiated the results of several earlier studies,2 3 4 5 6 7 which provided evidence for enhanced NO systems in young and adult SHR. The presence of severe hypertension in the face of a marked increase in the NO system may be indicative of enhanced NO inactivation. Superoxide and other reactive oxygen species (ROS) can avidly react with and inactivate NO.8 9 10 11 It is of note that several recent studies have provided compelling evidence for increased ROS activity in SHR.12 13 14 15 Therefore, the associated increased ROS activity can enhance NO inactivation and reduce bioactive NO. This can, in turn, contribute to the maintenance of hypertension and cause a compensatory upregulation of NO synthase (NOS) isotype expression. In fact, administration of the cell-permeable superoxide dismutase mimetic, tempol, has been recently shown to lower blood pressure and increase NO availability in SHR.14 We have recently shown that biologically active NO exerts a negative-feedback influence on NOS expression in cultured human endothelial cells.16 Thus, increased ROS-mediated inactivation of NO can potentially contribute to a compensatory upregulation of NOS via a reduction in NO bioavailability, as recently shown in lead-induced hypertension.11 17 The present study was undertaken to test the hypothesis that antioxidant therapy may alleviate hypertension and reverse the compensatory upregulation of NOS isotypes in SHR.


*    Methods
up arrowTop
up arrowAbstract
up arrowIntroduction
*Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Animals
Eight-week-old male SHR (Harlan Sprague Dawley Inc, Indianapolis, Ind) were housed in a temperature-controlled light-regulated space with 12-hour light and dark cycles. The animals were allowed free access to a low nitrate basic rat chow and water. The animals were randomly assigned to the lazaroid-treated and vehicle-treated control groups. The lazaroid-treated group received a potent antioxidant lazaroid compound, desmethyltirilazad (U7489G, UpJohn Inc), at 10 mg · kg-1 · d-1 by gastric gavage for 3 weeks. The placebo-treated SHR group received the inactive vehicle instead. A control group of age-matched male genetically normotensive Wistar-Kyoto rats (WKY) served as controls. To determine the possible effect of lazaroid therapy in genetically normotensive animals, the studies were repeated comparing 2 groups of WKY treated with lazaroid and placebo, as described for the SHR group. A minimum of 6 animals was included in each group. Timed urine collections were obtained by placing the rats in metabolic cages. Food was withdrawn, but water was provided the night before and during the collection period.

At the conclusion of the 3-week treatment period, the animals were anesthetized with intraperitoneal injections of pentobarbital sodium (Nembutal, 50 mg/kg). Blood was obtained by cardiac puncture, and brain, heart (left ventricle), thoracic aorta, and kidneys were immediately harvested, cleaned, and promptly frozen in liquid nitrogen. The samples were then stored at -70°C until they were processed.

Measurement of Arterial Pressure
Arterial pressure was measured by tail plethysmography as described in our earlier studies.18 Briefly conscious rats were placed on a heated pad in a temperature-controlled quiet space. They were allowed to rest for 15 minutes with the tail placed inside a tail cuff. The cuff was inflated and released several times to condition the animal to the procedure. Thereafter, 4 consecutive measurements were taken by a rat-tail blood pressure monitor, recorded by a student oscillograph (Harvard Apparatus Inc), and averaged for presentation.

Measurement of Total NOx
Urine nitrate and nitrite (NOx) concentration was measured by using the purge system of a model 270B nitric oxide analyzer (NOA228, Sievers Instruments Inc) in a manner that was identical to that described in our earlier studies.19

Tissue Preparation and Western Blot Analyses
Kidney, aorta, heart, and brain tissues were prepared for measurements of endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) protein abundance by Western blot analysis. The procedures were performed in a manner that was identical to that described in our previous studies using anti-eNOS, anti-iNOS, and anti-nNOS antibodies (Transduction Laboratories).20 21 Briefly, aorta, heart, brain, and kidney tissue protein preparations (50 µg for the aorta, heart, and brain; 100 µg for the kidney) were size-fractionated on 4% to 12% Tris-glycine gel (Novex) at 120 V for 3 hours. In preliminary experiments, we found that the given protein concentrations were within the linear range of detection for our Western blot technique. After electrophoresis, proteins were transferred onto Hybond-ECL membranes (Amersham Life Science Inc) at 400 mA for 120 minutes with the use of the Novex transfer system. The membrane was prehybridized in 10 mL buffer A (10 mmol/L Tris hydrochloride, pH 7.5, 100 mmol/L NaCl, 0.1% Tween 20, and 10% nonfat milk powder) for 1 hour and then hybridized for an additional 1-hour period in the same buffer containing 10 µL of the given anti-NOS monoclonal antibody (1:1000). The membrane was then washed for 30 minutes in a shaking bath, with the wash buffer (buffer A without nonfat milk) changed every 5 minutes before 1 hour of incubation in buffer A plus goat anti-mouse IgG-horseradish peroxidase at a final titer of 1:1000. Experiments were performed at room temperature. The washes were repeated before the membrane was developed with a light-emitting nonradioactive method using ECL reagent (Amersham Inc). The membrane was then subjected to autoluminography for 1 to 5 minutes. The autoluminographs were scanned with a laser densitometer (model PD1211, Molecular Dynamics) to determine the relative optical densities of the bands. In all instances, the membranes were stained with Ponceau stain before prehybridization. This step verified the uniformity of protein load and transfer efficiency across the test samples.

In an attempt to explore possible cross-reactivity between eNOS and iNOS in the vascular tissue, we probed cultured endothelial cell protein preparations for immunodetectable iNOS by Western blot. No detectable iNOS was found, whereas abundant eNOS was present in this preparation. This observation excludes discernible cross-reactivity with the antibodies used in this system. In addition, the experiments suggested that constitutively expressed iNOS in the vascular tissue is most likely contained in cells other than the endothelial lining.

To discern the approximate comparison of eNOS and iNOS protein abundance in the vascular, renal, and cardiac tissues, we carried a set of separate experiments in which simultaneous Western blots were obtained under identical conditions for both NOS isotypes. On every occasion, the optical densities of the iNOS bands were {approx}200% less than those of the corresponding eNOS bands. These findings suggest that constitutively expressed iNOS protein abundance is substantially less than that of eNOS. However, given the uncertainty regarding the antigen binding potency of the 2 antibodies, accurate assessment of relative quantities of the 2 enzymes is not possible by the methods used in the present study.

Data Analysis
ANOVA was used in statistical analysis of the data, which are presented as mean±SEM. A value of P<0.05 was considered significant.


*    Results
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowMethods
*Results
down arrowDiscussion
down arrowReferences
 
Blood Pressure and NOx Excretion
As expected, the placebo-treated SHR group exhibited a marked elevation in arterial blood pressure compared with the WKY control group. Antioxidant therapy with the lazaroid compound resulted in a significant amelioration of hypertension. In confirmation of our earlier study,1 compared with the WKY control group, the placebo-treated SHR group showed a significant increase in urinary excretion of NOx. Antioxidant therapy lowered the urinary NOx excretion in the lazaroid-treated SHR group toward values seen in the control animals. In contrast to the data obtained in the SHR group, lazaroid therapy had no effect on either blood pressure or urinary NOx excretion in the WKY group (Figure 1).



View larger version (36K):
[in this window]
[in a new window]
 
Figure 1. Systolic blood pressure and urinary excretion of NO metabolites (NOx) in placebo-treated and lazaroid (Lz)-treated WKY and SHR (n=6 in each group). *P<0.05.

Aorta NOS Isotypes
Compared with the WKY group, the placebo-treated SHR group showed a marked upregulation of eNOS and iNOS protein abundance in the aorta. Antioxidant therapy resulted in a significant attenuation of aorta eNOS and iNOS protein expressions in the lazaroid-treated SHR group (Figure 2). However, lazaroid therapy had no effect on either eNOS or iNOS expression in WKY aortas (Figure 3).



View larger version (26K):
[in this window]
[in a new window]
 
Figure 2. Representative Western blots and group data depicting thoracic aorta eNOS (top blots and graph) and iNOS (bottom blots and graph) protein abundance in WKY and in untreated SHR and Lz-treated SHR (SHR+Lz) (n=6 in each group). *P<0.01.



View larger version (43K):
[in this window]
[in a new window]
 
Figure 3. Representative Western blots and group data depicting eNOS, iNOS, and nNOS protein abundance in the kidney, aorta, heart, and brain of untreated and Lz-treated WKY (WKY+Lz) (n=6 in each group). No significant differences were found.

Kidney NOS Isotypes
Kidney tissue eNOS and iNOS protein abundance was markedly increased in the placebo-treated SHR group relative to the corresponding values found in the WKY control group. The upregulations of the kidney tissue eNOS and iNOS protein expressions were significantly attenuated by antioxidant therapy in the lazaroid-treated SHR group. As with eNOS and iNOS proteins, renal tissue nNOS protein abundance was significantly increased in the placebo-treated SHR group. However, the magnitude of the lazaroid-induced fall in renal nNOS protein expression was far less than that seen with eNOS and iNOS proteins (Figure 4). In contrast to data obtained in the SHR group, lazaroid therapy had no effect on either eNOS, iNOS, or nNOS in the kidneys of the WKY group (Figures 3).



View larger version (26K):
[in this window]
[in a new window]
 
Figure 4. Representative Western blots and group data depicting kidney tissue eNOS (top blots and graph) and iNOS (bottom blots and graph) protein abundance in WKY and in untreated SHR and SHR+Lz (n=6 in each group). *P<0.05

Brain nNOS Protein
Compared with the WKY control group, the placebo-treated SHR group showed a marked increase in brain tissue nNOS protein abundance. Lazaroid therapy caused a minimal reduction in immunodetectable nNOS protein abundance in the SHR brain and no effect in the WKY brain (Figures 3 and 5).



View larger version (30K):
[in this window]
[in a new window]
 
Figure 5. Representative Western blots and group data depicting brain (top blots and graph) and kidney (bottom blots and graph) nNOS protein abundance in WKY and in untreated SHR and SHR+Lz (n=6 in each group). *P<0.01 for WKY vs SHR; P>0.05 for SHR vs SHR-Lz.

Heart NOS Isotypes
The placebo-treated SHR exhibited a marked upregulation of cardiac eNOS and iNOS protein expressions. Antioxidant therapy caused a significant but partial reversal of the cardiac eNOS and iNOS protein elevations in the lazaroid-treated SHR. However, lazaroid therapy had no effect on cardiac tissue NOS isotype expressions in WKY (Figures 3 and 6).



View larger version (28K):
[in this window]
[in a new window]
 
Figure 6. Representative Western blots and group data depicting heart eNOS (top blots and graph) and iNOS (bottom blots and graph) protein abundance in WKY and in untreated SHR and SHR+Lz (n=6 in each group). *P<0.01.


*    Discussion
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowMethods
up arrowResults
*Discussion
down arrowReferences
 
Several recent studies have provided compelling evidence for increased ROS generation in the vascular tissues of SHR.13 22 23 24 For instance, using fluorescence microscopy, Suzuki et al23 have demonstrated enhanced superoxide production in mesenteric arterioles of SHR in vivo. Likewise Grunfeld et al24 have reported increased superoxide generation in cultured aortic endothelial cells from SHR compared with corresponding cells from WKY. Moreover, Cosentino et al13 have shown increased superoxide and hydrogen peroxide release in aortic strips prepared from SHR. ROS are thought to contribute to the generation and/or maintenance of hypertension in SHR by several mechanisms. These include inactivation of endothelium-derived NO,12 14 nonenzymatic generation of vasoconstrictive F2-isoprostanes from arachidonic acid peroxidation,15 and depletion of the NOS cofactor tetrahydrobiopterin.13 The role of oxidative stress in the genesis and maintenance of hypertension in SHR is supported by amelioration of hypertension with antioxidant administration.14 15 22 23 25 26

In addition to SHR, oxidative stress has been implicated in a variety of other hypertensive disorders, including lead-induced hypertension,11 18 27 28 uremic hypertension,19 cyclosporine-induced hypertension,29 30 salt-sensitive hypertension,31 32 preeclampsia,33 essential hypertension,34 35 36 37 and diabetes.38 39 In addition, long-term consumption of high-fat and highly refined sugar diets, which are known to cause oxidative stress,40 41 has been shown to produce hypertension in normotensive animals.42 43 Finally, we have recently shown that induction of oxidative stress by glutathione depletion leads to severe sustained hypertension and depressed NO availability in genetically normotensive Sprague-Dawley rats.44 Thus, oxidative stress appears to be a common feature of hypertensive disorders of diverse origins.

ROS avidly react with and inactivate NO.8 9 10 ROS-mediated NO inactivation can contribute to hypertension and endothelial dysfunction by limiting the availability of biologically active NO. Earlier studies have revealed that NO can rapidly inhibit NOS enzymatic activity, presumably by interacting with the iron core of the heme moiety of the enzyme.45 In addition, we have recently shown that NO exerts a negative-feedback role in the regulation of endothelial NOS expression.16 On the basis of these considerations, we hypothesized that upregulation of renal and vascular NOS isotypes found in our earlier study of SHR1 may be due to the ROS-mediated reduction of NO availability and, hence, diminished negative-feedback regulation of NOS expression. If true, amelioration of oxidative stress by antioxidant therapy should mitigate the upregulation of NOS isotypes in SHR.

In the present study, the untreated SHR group exhibited a significant elevation of arterial blood pressure, increased urinary NO metabolite excretion, and marked upregulation of renal, vascular, and cardiac eNOS and iNOS and of brain and kidney nNOS protein expressions. Administration of the potent antioxidant, desmethyltirilazad, for 3 weeks resulted in a significant amelioration of hypertension despite marked reductions in urinary NOx excretion and renal, vascular, and cardiac NOS isotype expressions. These data suggest that alleviation of oxidative stress by antioxidant therapy diminishes ROS-mediated NO inactivation and, thereby, raises the availability of bioactive NO in the treated SHR. The rise in the bioactive NO availability, in turn, enhances NO-mediated vasodilatory tone, which could, in part, account for the observed amelioration of hypertension. In addition, improved NO availability restores the NO-mediated negative-feedback regulation of NOS activity45 and protein expression16 and, thereby, reverses the compensatory upregulation of NOS isotypes in the treated SHR. The observed effects of antioxidant therapy on blood pressure and NO metabolism in SHR were not due to a nonspecific action of the drug used. The latter assertion is substantiated by the lack of any effect of lazaroid therapy on blood pressure, urinary NOx excretion, or tissue NOS isotype expressions in the normotensive WKY. The latter findings parallel those of our recent studies demonstrating that in the absence of oxidative stress, antioxidant therapy has no effect on blood pressure, urinary NOx excretion, or NOS expression.11 17 The results of the present study in SHR are consistent with those of our recent studies in rats with lead-induced hypertension, which is marked by oxidative stress and compensatory upregulation of renal and vascular NOS isotypes.11 17 18 Administration of desmethyltirilazad in animals with lead-induced hypertension reversed oxidative stress, improved NO availability, and ameliorated hypertension27 in a manner similar to that found in SHR in the present study. In a more recent series of studies, we found that amelioration of oxidative stress and hypertension with a vitamin E–fortified diet was coupled with enhanced NO availability and a reversal of compensatory upregulation of renal and vascular NOS isotype expressions in rats with lead-induced hypertension,11 17 mirroring the findings of the present study in SHR.

The untreated SHR exhibited a marked increase in urinary total NOx excretion despite avid ROS-mediated oxidation and sequestration of NO as peroxynitrite (ONOO-) and nitrated tyrosine and other molecules. These events are expected to lower rather than raise urinary NOx excretion. Although this is true for the unsteady-state phase, isomerization of ONOO- and turnover of the nitrated molecules will eventually lead to formation of NO3- and NO2-, which are excreted in the urine. Thus, during a steady-state condition, such as chronic hypertension, urinary NOx reflects NO production despite ongoing ROS-mediated inactivation of NO.

The antioxidant used in the present study was desmethyltirilazad, which is a powerful scavenger of various ROS and a potent inhibitor of lipid peroxidation.46 This compound and its closely related derivatives have been widely used to study the effect of oxidative stress in a wide range of disorders.46 In addition, we have used this agent in our earlier studies demonstrating the role of oxidative stress in the pathogenesis of uremic and lead-induced hypertension.19 27

Antioxidant therapy significantly ameliorated hypertension and partially reversed the upregulation of NOS isotypes in various tissues of SHR. However, it did not fully restore either blood pressure or NOS isotype expression to the levels found in the normal control animals. Increased shear stress and cyclic strain upregulate eNOS expression. In addition, both systemic hypertension47 48 and regional cerebral arterial hypertension induced by simulated microgravity49 increase nNOS expression in the brain. Thus, the residual elevation of NOS isotype expression in the lazaroid-treated SHR may be due to the moderate hypertension observed in these animals. The partial role of elevated blood pressure in the upregulation of NOS isotypes is evidenced by significant but incomplete reversal of renal and vascular NOS isotype expressions with different antihypertensive agents (angiotensin type 1 receptor blockers and calcium channel blockers) in this model (X.Q. Wang, N.D. Vaziri, unpublished data, 2000). Thus, both ROS-mediated attenuation of negative-feedback regulation of NOS by NO and increased shear stress associated with hypertension contribute to the upregulation of NOS isotypes in SHR.

In conclusion, hypertension in untreated SHR was accompanied by increased urinary excretion of NO metabolites and marked upregulations of renal, vascular, and cardiac NOS isotype expression, confirming our earlier study.1 Administration of the potent antioxidant compound desmethyltirilazad ameliorated hypertension, lowered urinary NO metabolite excretion, and attenuated the compensatory upregulation of NOS isotypes in the tested organs. These findings point to the role of oxidative stress in the pathogenesis of hypertension and disordered NO metabolism in SHR.


*    Acknowledgments
 
The authors wish to express their gratitude to Tania Tajalli for her assistance in this project.


*    Footnotes
 
Reprint requests to N.D. Vaziri, MD, MACP, Division of Nephrology and Hypertension, UCI Medical Center, 101 The City Drive, Orange, CA 92868.

Received June 5, 2000; first decision June 30, 2000; accepted July 6, 2000.


*    References
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowMethods
up arrowResults
up arrowDiscussion
*References
 
1. Vaziri ND, Ni Z, Oveisi F. Upregulation of renal and vascular nitric oxide synthase in young spontaneously hypertensive rats. Hypertension. 1998;31:1248–1254.[Abstract/Free Full Text]

2. Akiba Y, Yamaguchi N, Amano H, Fujii T, Fujimoto K, Suzuki T, Kawashima K. Role of nitric oxide in control of blood pressure in young and adult spontaneously hypertensive rats. Clin Exp Pharmacol Physiol Suppl. 1995;1:S142–S143.

3. Gil-Longo J, Fernandez-Grandal D, Alvarez M, Siera M, Orallo F. Study of in vivo and in vitro resting vasodilator nitric oxide tone in normotensive and genetically hypertensive rats. Eur J Pharmacol. 1996;310:175–183.[Medline] [Order article via Infotrieve]

4. Tomita T, Onda T, Mashiko S, Hamano M, Tomita I. Blood pressure-related changes of endothelium-dependent relaxation in the aorta from SHRSP at developmental ages of hypertension. Clin Exp Pharmacol Physiol Suppl. 1995;1:S139–S141.

5. Hayakawa H, Coffee K, Raij L. Nitric oxide activity is enhanced in the vasculature and renal medulla of spontaneously hypertensive rats, but fails to control hypertension. J Am Soc Nephrol. 1996;7:1562. Abstract.

6. Wu CC, Hong HJ, Chou TC, Ding YA, Yen MH. Evidence for inducible nitric oxide synthase in spontaneously hypertensive rats. Biochem Biophys Res Commun. 1996;228:459–466.[Medline] [Order article via Infotrieve]

7. Hayakawa H, Raij L. Nitric oxide synthase activity and renal injury in genetic hypertension. Hypertension. 1998;31(pt 2):266–270.

8. Halliwell B. What nitrates tyrosine?: is nitrotyrosine specific as a biomarker of peroxynitrite formation in vivo? FEBS Lett.. 1997;411:157–160.[Medline] [Order article via Infotrieve]

9. Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly: Am J Physiol.. 1996;271:C1424–C1437.[Abstract/Free Full Text]

10. Eiserich JP, Butler J, van der Vliet A, Cross CE, Halliwell B. Nitric oxide rapidly scavenges tyrosine and tryptophan radicals. Biochem J. 1995;310:745–749.

11. Vaziri ND, Liang K, Ding Y. Increased nitric oxide inactivation by reactive oxygen species in lead-induced hypertension. Kidney Int. 1999;56:1492–1498.[Medline] [Order article via Infotrieve]

12. Tschudi MR, Mesaros S, Luscher TF, Malinski T. Direct in situ measurement of nitric oxide in mesenteric resistance arteries: increased decomposition by superoxide in hypertension. Hypertension. 1996;27:32–35.[Abstract/Free Full Text]

13. Cosentino F, Patton S, D’Uscio LV, Werner ER, Werner-Felmayer G, Moreau P, Malinski T, Luscher TF. Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats. J Clin Invest. 1998;101:1530–1537.[Medline] [Order article via Infotrieve]

14. Schnackenberg CG, Welch WJ, Wilcox CS. Normalization of blood pressure and renal vascular resistance in SHR with a membrane-permeable superoxide dismutase mimetic: role of nitric oxide. Hypertension. 1998;32:59–64.[Abstract/Free Full Text]

15. Schnackenberg CG, Wilcox CS. Two-week administration of tempol attenuates both hypertension and renal excretion of 8-isoprostaglandin F2{alpha}. Hypertension. 1999;33:424–428.[Abstract/Free Full Text]

16. Vaziri ND, Wang XQ. cGMP-mediated negative-feedback regulation of endothelial nitric oxide synthase expression by nitric oxide. Hypertension. 1999;34:1237–1241.[Abstract/Free Full Text]

17. Vaziri ND, Ding Y, Ni Z. Nitric oxide synthase expression in the course of lead-induced hypertension. Hypertension. 1999;34:558–562.[Abstract/Free Full Text]

18. Gonick HC, Ding Y, Bondy SC, Ni Z, Vaziri ND. Lead-induced hypertension: interplay of nitric oxide and reactive oxygen species. Hypertension. 1997;30:1487–1492.[Abstract/Free Full Text]

19. Vaziri ND, Oveisi F, Ding Y. Role of increased oxygen free radical activity in the pathogenesis of uremic hypertension. Kidney Int. 1998;53:1748–1754.[Medline] [Order article via Infotrieve]

20. Vaziri ND, Ni Z, Zhang YP, Ruzicks EP, Maleki P, Ding Y. Depressed renal and vascular nitric oxide synthase expression in cyclosporine-induced hypertension. Kidney Int. 1998;54:482–491.[Medline] [Order article via Infotrieve]

21. Vaziri ND, Ni Z, Wang XQ, Oveisi F, Zhou XJ. Downregulation of nitric oxide synthase in chronic renal insufficiency: role of excess PTH. Am J Physiol. 1998;274:F642–F649.

22. Suzuki H, DeLano FA, Parks DA, Jamshidi N, Granger DN, Ishii H, Suematsu M, Zweifach BW, Schmid-Schonbein GW. Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats. Proc Natl Acad Sci U S A. 1998;95:4754–4759.[Abstract/Free Full Text]

23. Suzuki H, Swei A, Zweifach BW, Schmid-Schonbein GW. In vivo evidence for microvascular oxidative stress in spontaneously hypertensive rats: hydroethidine microfluorography. Hypertension. 1995;25:1083–1089.[Abstract/Free Full Text]

24. Grunfeld S, Hamilton CA, Mesaros S, McClain SW, Dominiczak AF, Bohr DF, Malinski T. Role of superoxide in the depressed nitric oxide production by the endothelium of genetically hypertensive rats. Hypertension. 1995;26:854–857.[Abstract/Free Full Text]

25. Yoshioka M, Aoyama K, Matsushita T. Effects of ascorbic acid on blood pressure and ascorbic acid metabolism in spontaneously hypertensive rats. Int J Vitam Nutr Res. 1985;55:301–307.[Medline] [Order article via Infotrieve]

26. Nakazono K, Watanabe N, Matsuno K, Sasaki J, Sato T, Inque M. Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci U S A. 1991;88:10045–10048.[Abstract/Free Full Text]

27. Vaziri ND, Ding Y, Ni Z, Gonick HC. Altered nitric oxide metabolism and increased oxygen free radical activity in lead-induced hypertension: effect of lazaroid therapy. Kidney Int. 1997;52:1042–1046.[Medline] [Order article via Infotrieve]

28. Ding Y, Vaziri ND, Gonick HC. Lead-induced hypertension, II: response to sequential infusions of L-arginine, superoxide dismutase, and nitroprusside. Environ Res. 1998;76:107–113.[Medline] [Order article via Infotrieve]

29. Navarro-Antolin J, Hernandez-Perera O, Lopez-Ongil S, Rodriguez-Puyol M, Rodriguez-Puyol D, Lamas S. CsA and FK506 up-regulate eNOS expression: role of reactive oxygen species and AP-1. Kidney Int Suppl. 1998;68:S20–S24.[Medline] [Order article via Infotrieve]

30. Lopez-Ongil S, Hernandez-Perera O, Navarro-Antolin J, Perez de Lema G, Rodriguez-Puyol M, Lamas S, Rodriguez-Puyol D. Role of reactive oxygen species in the signaling cascade of cyclosporine A-mediated up-regulation of eNOS in vascular endothelial cells. Br J Pharmacol. 1998;124:447–454.[Medline] [Order article via Infotrieve]

31. Atarashi K, Ishiyama A, Takagi M, Minami M, Kimura K, Goto A, Omata M. Vitamin E ameliorates the renal injury of Dahl salt-sensitive rats. Am J Hypertens. 1997;10:116S–119S.[Medline] [Order article via Infotrieve]

32. Swei A, Lacy F, DeLano FA, Schmid-Schonbein GW. Oxidative stress in the Dahl hypertensive rat. Hypertension. 1997;30:1628–1633.[Abstract/Free Full Text]

33. Roggensack AM, Zhang Y, Davidge ST. Evidence for peroxynitrite formation in the vasculature of women with preeclampsia. Hypertension. 1999;33:83–89.[Abstract/Free Full Text]

34. Kitiyakara C, Wilcox C. Antioxidants for hypertension. Curr Opin Nephrol Hypertens. 1998;7:531–538.[Medline] [Order article via Infotrieve]

35. Lacy F, O’Conner DT, Schmid-Schonbein GW. Plasma hydrogen peroxide production in hypertensives and normotensive subjects at genetic risk of hypertension. J Hypertens. 1998;16:291–303.[Medline] [Order article via Infotrieve]

36. Kumar DV, Das UN. Are free radicals involved in the pathobiology of human essential hypertension? Free Radic Res Commun. 1993;19:59–66.[Medline] [Order article via Infotrieve]

37. Tse WY, Maxwell SR, Thomason H, Blann A, Thorpe GH, Waite M, Holder R. Antioxidant status in controlled and uncontrolled hypertension and its relationship to endothelial damage. J Hum Hypertens. 1994;89:843–849.

38. Giugliano D, Ceriello A, Paolisso G. Diabetes mellitus, hypertension, and cardiovascular disease: which role for oxidative stress? Metabolism. 1995;44:363–368.[Medline] [Order article via Infotrieve]

39. Orie NN, Zidek W, Tepel M. Reactive oxygen species in essential hypertension and non-insulin-dependent diabetes mellitus. Am J Hypertens. 1999;12:1169–1174.[Medline] [Order article via Infotrieve]

40. Faure P, Rossini E, Lafond JL, Richard MJ, Favier A, Halimi S. Vitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose diets. J Nutr. 1997;127:103–107.[Abstract/Free Full Text]

41. Aliev G, Bodin P, Burnstock G. Free radical generators cause changes in endothelial and inducible nitric oxide synthases and endothelin-1 immunoreactivity in endothelial cells from hyperlipidemic rabbits. Mol Genet Metab. 1998;63:191–197.[Medline] [Order article via Infotrieve]

42. Roberts CK, Vaziri ND, Wang XQ, Barnard RJ. Enhanced NO inactivation and hypertension induced by a high-fat, refined carbohydrate diet. Hypertension.. 2000;36:423–429.[Abstract/Free Full Text]

43. Barnard RJ, Roberts CK, Varon SM, Berger JJ. Diet-induced insulin resistance precedes other aspects of metabolic syndrome. J Appl Physiol. 1999;84:1311–1315.[Abstract/Free Full Text]

44. Vaziri ND, Wang XQ, Oveisi F, Rad B. Induction of oxidative stress by glutathione depletion causes hypertension in normal rats. Hypertension. 2000;36:142–146.[Abstract/Free Full Text]

45. Buga GM, Griscavage JM, Rogers NE, Ignarro LJ. Negative feed-back regulation of endothelial cell function by nitric oxide. Circ Res. 1993;73:808–812.[Abstract/Free Full Text]

46. Clark WM, Hazel S, Coull BM. Lazaroids: CNS pharmacology and current research. Drugs. 1995;50:971–893.[Medline] [Order article via Infotrieve]

47. Ye S, Nosrati S, Campese VM. Nitric oxide (NO) modulates the neurogenic control of blood pressure in rats with chronic renal failure. J Clin Invest. 1997;99:540–548.[Medline] [Order article via Infotrieve]

48. Ni Z, Oveisi F, Vaziri ND. Nitric oxide synthase isotype expression in salt-sensitive and salt-resistant Dahl rats. Hypertension. 1999;34:552–557.[Abstract/Free Full Text]

49. Vaziri ND, Ding Y, Sangha DS, Purdy RE. Up-regulation of NOS by simulated microgravity, potential cause of orthostatic intolerance. J Appl Physiol. 2000;89:338–344.[Abstract/Free Full Text]




This article has been cited by other articles:


Home page
ANGIOLOGYHome page
S. Nambiar, S. Viswanathan, B. Zachariah, N. Hanumanthappa, and Sridhar Gopalakrishna Magadi
Oxidative Stress in Prehypertension: Rationale for Antioxidant Clinical Trials
Angiology, April 1, 2009; 60(2): 221 - 234.
[Abstract] [PDF]


Home page
Journal of Renin-Angiotensin-Aldosterone SystemHome page
M. Labios, M. Martinez, F. Gabriel, V. Guiral, F. Dasi, B. Beltran, and A. Munoz
Superoxide dismutase and catalase anti-oxidant activity in leucocyte lysates from hypertensive patients: effects of eprosartan treatment
Journal of Renin-Angiotensin-Aldosterone System, March 1, 2009; 10(1): 24 - 30.
[Abstract] [PDF]


Home page
J. Appl. Physiol.Home page
R. Zhang, Y.-G. Bai, L.-J. Lin, J.-X. Bao, Y.-Y. Zhang, H. Tang, J.-H. Cheng, G.-L. Jia, X.-L. Ren, and J. Ma
Blockade of AT1 receptor partially restores vasoreactivity, NOS expression, and superoxide levels in cerebral and carotid arteries of hindlimb unweighting rats
J Appl Physiol, January 1, 2009; 106(1): 251 - 258.
[Abstract] [Full Text] [PDF]


Home page
Evid Based Complement Alternat MedHome page
H. S. Hwang, Y. S. Kim, Y. H. Ryu, J. E. Lee, Y. S. Lee, E. J. Yang, M. S. Lee, and S.-M. Choi
Electroacupuncture Delays Hypertension Development through Enhancing NO/NOS Activity in Spontaneously Hypertensive Rats
Evid. Based Complement. Altern. Med., October 7, 2008; (2008) nen064v1.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
H. Li, M. Hortmann, A. Daiber, M. Oelze, M. A. Ostad, P. M. Schwarz, H. Xu, N. Xia, A. L. Kleschyov, C. Mang, et al.
Cyclooxygenase 2-Selective and Nonselective Nonsteroidal Anti-Inflammatory Drugs Induce Oxidative Stress by Up-Regulating Vascular NADPH Oxidases
J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 745 - 753.
[Abstract] [Full Text] [PDF]


Home page
Diabetes CareHome page
E. Grossman
Does Increased Oxidative Stress Cause Hypertension?
Diabetes Care, February 1, 2008; 31(Supplement_2): S185 - S189.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. J. Pinho, V. Pinto, M. P. Serrao, P. A. Jose, and P. Soares-da-Silva
Underexpression of the Na+-dependent neutral amino acid transporter ASCT2 in the spontaneously hypertensive rat kidney
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R538 - R547.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
G. Cambonie, B. Comte, C. Yzydorczyk, T. Ntimbane, N. Germain, N. L. O. Le, P. Pladys, C. Gauthier, I. Lahaie, D. Abran, et al.
Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1236 - R1245.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
M. Franco, F. Martinez, B. Rodriguez-Iturbe, R. J. Johnson, J. Santamaria, A. Montoya, T. Nepomuceno, R. Bautista, E. Tapia, and J. Herrera-Acosta
Angiotensin II, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension
Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1281 - F1287.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. Paliege, A. Parsumathy, D. Mizel, T. Yang, J. Schnermann, and S. Bachmann
Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R694 - R700.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
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]


Home page
J. Pharmacol. Exp. Ther.Home page
N. D. Vaziri, Y. Ding, Z. Ni, and C. H. Barton
Bradykinin Down-Regulates, Whereas Arginine Analogs Up-Regulates, Endothelial Nitric-Oxide Synthase Expression in Coronary Endothelial Cells
J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 121 - 126.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
S. Racasan, B. Braam, H. A. Koomans, and J. A. Joles
Programming blood pressure in adult SHR by shifting perinatal balance of NO and reactive oxygen species toward NO: the inverted Barker phenomenon
Am J Physiol Renal Physiol, April 1, 2005; 288(4): F626 - F636.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
S. Adler and H. Huang
Oxidant stress in kidneys of spontaneously hypertensive rats involves both oxidase overexpression and loss of extracellular superoxide dismutase
Am J Physiol Renal Physiol, November 1, 2004; 287(5): F907 - F913.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
B. H. Jeon, G. Gupta, Y. C. Park, B. Qi, A. Haile, F. A. Khanday, Y.-X. Liu, J.-M. Kim, M. Ozaki, A. R. White, et al.
Apurinic/Apyrmidinic Endonuclease 1 Regulates Endothelial NO Production and Vascular Tone
Circ. Res., October 29, 2004; 95(9): 902 - 910.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
K. Sato, M. Kihara, T. Hashimoto, K. Matsushita, Y.-I. Koide, K. Tamura, N. Hirawa, Y. Toya, A. Fukamizu, and S. Umemura
Alterations in Renal Endothelial Nitric Oxide Synthase Expression by Salt Diet in Angiotensin Type-1a Receptor Gene Knockout Mice
J. Am. Soc. Nephrol., July 1, 2004; 15(7): 1756 - 1763.
[Abstract] [Full Text] [PDF]


Home page
Exp PhysiolHome page
X. C. Wu and E. J. Johns
Interactions between nitric oxide and superoxide on the neural regulation of proximal fluid reabsorption in hypertensive rats
Exp Physiol, May 1, 2004; 89(3): 255 - 261.
[Abstract] [Full Text] [PDF]


Home page
FASEB J.Home page
S. FOGLI, P. NIERI, and M. C. BRESCHI
The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage
FASEB J, April 1, 2004; 18(6): 664 - 675.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
B. Rodriguez-Iturbe, N. D. Vaziri, J. Herrera-Acosta, and R. J. Johnson
Oxidative stress, renal infiltration of immune cells, and salt-sensitive hypertension: all for one and one for all
Am J Physiol Renal Physiol, April 1, 2004; 286(4): F606 - F616.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
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]


Home page
J. Nutr.Home page
H. Negishi, J.-W. Xu, K. Ikeda, M. Njelekela, Y. Nara, and Y. Yamori
Black and Green Tea Polyphenols Attenuate Blood Pressure Increases in Stroke-Prone Spontaneously Hypertensive Rats
J. Nutr., January 1, 2004; 134(1): 38 - 42.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
M. Nava, Y. Quiroz, N. Vaziri, and B. Rodriguez-Iturbe
Melatonin reduces renal interstitial inflammation and improves hypertension in spontaneously hypertensive rats
Am J Physiol Renal Physiol, March 1, 2003; 284(3): F447 - F454.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
S. Ulker, P. P. McKeown, and U. Bayraktutan
Vitamins Reverse Endothelial Dysfunction Through Regulation of eNOS and NAD(P)H Oxidase Activities
Hypertension, March 1, 2003; 41(3): 534 - 539.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
J. Y.H. Chan, L.-L. Wang, Y.-M. Chao, and S. H.H. Chan
Downregulation of Basal iNOS at the Rostral Ventrolateral Medulla Is Innate in SHR
Hypertension, March 1, 2003; 41(3): 563 - 570.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
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]


Home page
HypertensionHome page
B. Rodriguez-Iturbe, C.-D. Zhan, Y. Quiroz, R. K. Sindhu, and N. D. Vaziri
Antioxidant-Rich Diet Relieves Hypertension and Reduces Renal Immune Infiltration in Spontaneously Hypertensive Rats
Hypertension, February 1, 2003; 41(2): 341 - 346.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
V. Alvarez, Y. Quiroz, M. Nava, H. Pons, and B. Rodriguez-Iturbe
Overload proteinuria is followed by salt-sensitive hypertension caused by renal infiltration of immune cells
Am J Physiol Renal Physiol, November 1, 2002; 283(5): F1132 - F1141.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
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]


Home page
ChestHome page
R. C. Sampaio, J. E. Tanus-Santos, S. E. S. F. C. Melo, S. Hyslop, K. G. Franchini, I. M. Luca, and H. Moreno Jr
Hypertension Plus Diabetes Mimics the Cardiomyopathy Induced by Nitric Oxide Inhibition in Rats
Chest, October 1, 2002; 122(4): 1412 - 1420.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
S. Adler and H. Huang
Impaired Regulation of Renal Oxygen Consumption in Spontaneously Hypertensive Rats
J. Am. Soc. Nephrol., July 1, 2002; 13(7): 1788 - 1794.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
X. J. Zhou, N. D. Vaziri, X. Q. Wang, F. G. Silva, and Z. Laszik
Nitric Oxide Synthase Expression in Hypertension Induced by Inhibition of Glutathione Synthase
J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 762 - 767.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
T. Kishi, Y. Hirooka, K. Ito, K. Sakai, H. Shimokawa, and A. Takeshita
Cardiovascular Effects of Overexpression of Endothelial Nitric Oxide Synthase in the Rostral Ventrolateral Medulla in Stroke-Prone Spontaneously Hypertensive Rats
Hypertension, February 1, 2002; 39(2): 264 - 268.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
N. D. Vaziri, Z. Ni, F. Oveisi, K. Liang, and R. Pandian
Enhanced Nitric Oxide Inactivation and Protein Nitration by Reactive Oxygen Species in Renal Insufficiency
Hypertension, January 1, 2002; 39(1): 135 - 141.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
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]


Home page
HypertensionHome page
X. Chen, R. M. Touyz, J. B. Park, and E. L. Schiffrin
Antioxidant Effects of Vitamins C and E Are Associated With Altered Activation of Vascular NADPH Oxidase and Superoxide Dismutase in Stroke-Prone SHR
Hypertension, September 1, 2001; 38(3): 606 - 611.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
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]


This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vaziri, N. D.
Right arrow Articles by Trnavsky-Hobbs, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vaziri, N. D.
Right arrow Articles by Trnavsky-Hobbs, D. L.
Related Collections
Right arrow Biochemistry and metabolism
Right arrow Other hypertension
Right arrow Hypertension - basic studies
Right arrow Coagulation and fibronolysis
Right arrow Genetics of cardiovascular disease
Right arrow Oxidant stress
Right arrow Endothelium/vascular type/nitric oxide