From the Division of Nephrology, Department of Medicine, University of
California at Irvine.
Abstract—The available data on the
role of the L-arginine/nitric oxide (NO) pathway in the
genesis of hypertension in spontaneously hypertensive rats (SHR) are
limited and contradictory. In an attempt to address this issue, male
SHR were studied during the early phase of evolution of hypertension
(age 8 to 12 weeks) to distinguish the primary changes of NO
metabolism from those caused by advanced hypertension,
vasculopathy, and aging late in the course of the disease. A group of
age-matched male Wistar-Kyoto rats (WKY) served as controls. The SHR
exhibited a marked rise in arterial blood pressure and a
significant increase in urinary excretion and plasma concentration of
NO metabolites (nitrite/nitrate [NOx]). Likewise, the SHR showed a
significant elevation of thoracic aorta NO synthase (NOS) activity
coupled with significant increases of kidney, aorta, inducible NOS
(iNOS), and endothelial NOS (eNOS) proteins. In an
attempt to determine whether the enhanced L-arginine/NO
pathway is a consequence of hypertension, studies were repeated using
3-week-old animals before the onset of hypertension. The study revealed
significant increases in urinary NOx excretion as well as vascular eNOS
and renal iNOS proteins. In conclusion, the L-arginine/NO
pathway is upregulated in young SHR both before and after the onset of
hypertension. Thus, development of hypertension is not due to a primary
impairment of NO production in SHR. On the contrary, NO
production is increased in young SHR both before and after the
onset of hypertension.
© 1998 American Heart Association, Inc.
Scientific Contributions
Upregulation of Renal and Vascular Nitric Oxide Synthase in Young Spontaneously Hypertensive Rats
Key Words: nitric oxide • nitric oxide synthase • endothelium-derived relaxing factor • kidney
This article has been cited by other articles:
 |
|
 |
|
  H. Macarthur, T. C. Westfall, and G. H. Wilken Oxidative stress attenuates NO-induced modulation of sympathetic neurotransmission in the mesenteric arterial bed of spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H183 - H189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Patterson, J. J. Mullins, and K. D. Mitchell Renoprotective effects of neuronal NOS-derived nitric oxide and cyclooxygenase-2 metabolites in transgenic rats with inducible malignant hypertension Am J Physiol Renal Physiol, January 1, 2008; 294(1): F205 - F211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Koeners, E. E. van Faassen, S. Wesseling, M. de Sain-van der Velden, H. A. Koomans, B. Braam, and J. A. Joles Maternal Supplementation With Citrulline Increases Renal Nitric Oxide in Young Spontaneously Hypertensive Rats and Has Long-Term Antihypertensive Effects Hypertension, December 1, 2007; 50(6): 1077 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. E. Rush, J. Quadrilatero, A. S. Levy, and R. J. Ford Chronic Resveratrol Enhances Endothelium-Dependent Relaxation but Does Not Alter eNOS Levels in Aorta of Spontaneously Hypertensive Rats Experimental Biology and Medicine, June 1, 2007; 232(6): 814 - 822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Bai, S. Ye, R. Mortazavi, V. Campese, and N. D. Vaziri Effect of renal injury-induced neurogenic hypertension on NO synthase, caveolin-1, AKt, calmodulin and soluble guanylate cyclase expressions in the kidney Am J Physiol Renal Physiol, March 1, 2007; 292(3): F974 - F980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Vargas, J. M. Moreno, I. Rodriguez-Gomez, R. Wangensteen, A. Osuna, M. Alvarez-Guerra, and J. Garcia-Estan Vascular and renal function in experimental thyroid disorders Eur. J. Endocrinol., February 1, 2006; 154(2): 197 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Sommer, T. J. Berndt, E. Frank, J. B. Patel, M. M. Redfield, X. Dong, M. D. Griffin, J. P. Grande, J. M. A. van Deursen, G. C. Sieck, et al. Elevated blood pressure and cardiac hypertrophy after ablation of the gly96/IEX-1 gene J Appl Physiol, February 1, 2006; 100(2): 707 - 716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Bevers, B. Braam, J. A. Post, A. J. van Zonneveld, T. J. Rabelink, H. A. Koomans, M. C. Verhaar, and J. A. Joles Tetrahydrobiopterin, but Not L-Arginine, Decreases NO Synthase Uncoupling in Cells Expressing High Levels of Endothelial NO Synthase Hypertension, January 1, 2006; 47(1): 87 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-F. Lam, T. E. Peterson, A. J. Croatt, K. A. Nath, and Z. S. Katusic Functional adaptation and remodeling of pulmonary artery in flow-induced pulmonary hypertension Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2334 - H2341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Rodriguez-Iturbe, A. Ferrebuz, V. Vanegas, Y. Quiroz, S. Mezzano, and N. D. Vaziri Early and Sustained Inhibition of Nuclear Factor-{kappa}B Prevents Hypertension in Spontaneously Hypertensive Rats J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 51 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vera, M. Galisteo, I. C. Villar, M. Sanchez, A. Zarzuelo, F. Perez-Vizcaino, and J. Duarte Soy Isoflavones Improve Endothelial Function in Spontaneously Hypertensive Rats in an Estrogen-Independent Manner: Role of Nitric-Oxide Synthase, Superoxide, and Cyclooxygenase Metabolites J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1300 - 1309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 T. Munzel, A. Daiber, V. Ullrich, and A. Mulsch Vascular Consequences of Endothelial Nitric Oxide Synthase Uncoupling for the Activity and Expression of the Soluble Guanylyl Cyclase and the cGMP-Dependent Protein Kinase Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1551 - 1557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
L. L. Kolo, T. C. Westfall, and H. Macarthur Modulation of neurotransmitter release by NO is altered in mesenteric arterial bed of spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1842 - H1847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Racasan, B. Braam, D. M. van der Giezen, R. Goldschmeding, P. Boer, H. A. Koomans, and J. A. Joles Perinatal L-Arginine and Antioxidant Supplements Reduce Adult Blood Pressure in Spontaneously Hypertensive Rats Hypertension, July 1, 2004; 44(1): 83 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Graham and J. W. E. Rush Exercise training improves aortic endothelium-dependent vasorelaxation and determinants of nitric oxide bioavailability in spontaneously hypertensive rats J Appl Physiol, June 1, 2004; 96(6): 2088 - 2096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 D. M. Attia, O. Feron, R. Goldschmeding, L. H. Radermakers, N. D. Vaziri, P. Boer, J.-L. Balligand, H. A. Koomans, and J. A. Joles Hypercholesterolemia in Rats Induces Podocyte Stress and Decreases Renal Cortical Nitric Oxide Synthesis via an Angiotensin II Type 1 Receptor-Sensitive Mechanism J. Am. Soc. Nephrol., April 1, 2004; 15(4): 949 - 957. [Abstract] [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]
|
|
|
|
|
|
S. Ulker, D. McMaster, P. P. McKeown, and U. Bayraktutan Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation Cardiovasc Res, August 1, 2003; 59(2): 488 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Racasan, J. A. Joles, P. Boer, H. A. Koomans, and B. Braam NO dependency of RBF and autoregulation in the spontaneously hypertensive rat Am J Physiol Renal Physiol, July 1, 2003; 285(1): F105 - F112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Roberts, N. D. Vaziri, R. K. Sindhu, and R. J. Barnard A high-fat, refined-carbohydrate diet affects renal NO synthase protein expression and salt sensitivity J Appl Physiol, March 1, 2003; 94(3): 941 - 946. [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]
|
|
|
|
|
|
L. V. Rossoni, M. Salaices, M. Miguel, A. M. Briones, L. A. Barker, D. V. Vassallo, and M. J. Alonso Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2110 - H2118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. Kagota, A. Tamashiro, Y. Yamaguchi, K. Nakamura, and M. Kunitomo High Salt Intake Impairs Vascular Nitric Oxide/Cyclic Guanosine Monophosphate System in Spontaneously Hypertensive Rats J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 344 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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. Wiemer, G. Itter, T. Malinski, and W. Linz Decreased Nitric Oxide Availability in Normotensive and Hypertensive Rats With Failing Hearts After Myocardial Infarction Hypertension, December 1, 2001; 38(6): 1367 - 1371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Chen, D. Li, T. Saldeen, and J. L. Mehta TGF-{beta}1 modulates NOS expression and phosphorylation of Akt/PKB in rat myocytes exposed to hypoxia-reoxygenation Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1035 - H1039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. D. Vaziri, Y. Ding, and Z. Ni Compensatory Up-Regulation of Nitric-Oxide Synthase Isoforms in Lead-Induced Hypertension; Reversal by a Superoxide Dismutase-Mimetic Drug J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 679 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. KOHLER, R. KREUTZ, A. GRUNDIG, L. ROTHERMUND, C. YAGIL, Y. YAGIL, A. R. PRIES, and J. HOYER Impaired Function of Endothelial Pressure-Activated Cation Channel in Salt-Sensitive Genetic Hypertension J. Am. Soc. Nephrol., August 1, 2001; 12(8): 1624 - 1629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ichihara, M. Hayashi, N. Hirota, and T. Saruta Superoxide Inhibits Neuronal Nitric Oxide Synthase Influences on Afferent Arterioles in Spontaneously Hypertensive Rats Hypertension, February 1, 2001; 37(2): 630 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. D. Vaziri, Z. Ni, F. Oveisi, and D. L. Trnavsky-Hobbs Effect of Antioxidant Therapy on Blood Pressure and NO Synthase Expression in Hypertensive Rats Hypertension, December 1, 2000; 36(6): 957 - 964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Roberts, N. D. Vaziri, X. Q. Wang, and R. J. Barnard Enhanced NO Inactivation and Hypertension Induced by a High-Fat, Refined-Carbohydrate Diet Hypertension, September 1, 2000; 36(3): 423 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. D. Vaziri, Y. Ding, D. S. Sangha, and R. E. Purdy Upregulation of NOS by simulated microgravity, potential cause of orthostatic intolerance J Appl Physiol, July 1, 2000; 89(1): 338 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Safar, J. Blacher, J. J. Mourad, and G. M. London Stiffness of Carotid Artery Wall Material and Blood Pressure in Humans : Application to Antihypertensive Therapy and Stroke Prevention Stroke, March 1, 2000; 31(3): 782 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Sangha, N. D. Vaziri, Y. Ding, and R. E. Purdy Vascular hyporesponsiveness in simulated microgravity: role of nitric oxide-dependent mechanisms J Appl Physiol, February 1, 2000; 88(2): 507 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Mathew, N. Y.-T. Fan, N. Yuan, P. N. Chander, M. H. Gewitz, and C. T. Stier Jr. Inhibition of NOS enhances pulmonary vascular changes in stroke-prone spontaneously hypertensive rats Am J Physiol Lung Cell Mol Physiol, January 1, 2000; 278(1): L81 - L89. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Chin, K. N. Pandey, S.-J. Shi, H. Kobori, C. Moreno, and L. G. Navar Increased activity and expression of Ca2+-dependent NOS in renal cortex of ANG II-infused hypertensive rats Am J Physiol Renal Physiol, November 1, 1999; 277(5): F797 - F804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Busse and I. Fleming A critical look at cardiovascular translational research Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H1655 - H1660. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zicha and J. Kunes Ontogenetic Aspects of Hypertension Development: Analysis in the Rat Physiol Rev, October 1, 1999; 79(4): 1227 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ni, F. Oveisi, and N. D. Vaziri Nitric Oxide Synthase Isotype Expression in Salt-Sensitive and Salt-Resistant Dahl Rats Hypertension, October 1, 1999; 34(4): 552 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. D. Vaziri, Y. Ding, and Z. Ni Nitric Oxide Synthase Expression in the Course of Lead-Induced Hypertension Hypertension, October 1, 1999; 34(4): 558 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Linz, P. Wohlfart, B. A Scholkens, T. Malinski, and G. Wiemer Interactions among ACE, kinins and NO Cardiovasc Res, August 15, 1999; 43(3): 549 - 561. [Full Text] [PDF]
|
|
|
|
|
|
W. J. Welch, A. Tojo, J.-U. Lee, D. G. Kang, C. G. Schnackenberg, and C. S. Wilcox Nitric oxide synthase in the JGA of the SHR: expression and role in tubuloglomerular feedback Am J Physiol Renal Physiol, July 1, 1999; 277(1): F130 - F138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Q. Wang and N. D. Vaziri Erythropoietin Depresses Nitric Oxide Synthase Expression by Human Endothelial Cells Hypertension, March 1, 1999; 33(3): 894 - 899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Schnackenberg and C. S. Wilcox Two-Week Administration of Tempol Attenuates Both Hypertension and Renal Excretion of 8-Iso Prostaglandin F2{alpha} Hypertension, January 1, 1999; 33(1): 424 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ichihara, J. D. Imig, and L. G. Navar Neuronal Nitric Oxide Synthase-Dependent Afferent Arteriolar Function in Angiotensin II-Induced Hypertension Hypertension, January 1, 1999; 33(1): 462 - 466. [Abstract] [Full Text] [PDF]
|
|