(Hypertension. 1998;31:189.)
© 1998 American Heart Association, Inc.
Workshop on Vascular Biology & Hypertension: From Molecules to Humans |
Nitric Oxide in Hypertension: Relationship With Renal Injury and Left Ventricular Hypertrophy
From the Department of Medicine, Veterans Affairs Medical Center and University of Minnesota Medical School, Minnesota, Minn.
Correspondence to Leopoldo Raij, MD, Nephrology/Hypertension (111J), VA Medical Center, One Veterans Drive, Minneapolis, MN 55417. E-mail raijx001{at}maroon.tc.umn.edu
Hypertension is accompanied by architectural changes in the kidney, heart, and vessels that are often maladaptive and can eventually contribute to end-organ disease such as renal failure, heart failure, and coronary disease. Nitric oxide, an endogenous vasodilator and antithrombotic agent synthesized in the endothelium by a constitutive nitric oxide synthase, inhibits growth-related responses to injury in vascular cells. Specifically, in the presence of hypertension, nitric oxide may work in the kidney by inhibiting both mesangial cell hypertrophy and hyperplasia as well as synthesis of extracellular matrix and in the heart and systemic vessels by modulating smooth muscle cell hypertrophy and hyperplasia. The effects of nitric oxide are antagonistic of the effects of angiotensin II. Shear stress and cyclic strain, physical forces known to operate in hypertension, are accompanied by increases in endothelial nitric oxide synthase expression, nitric oxide synthase protein, and nitric oxide synthase activity in endothelial cells. Experimental studies using genetic models of hypertension show a variation in hypertension-modulated vascular nitric oxide synthase activity in different strains of rats. These studies suggest that upregulation of vascular nitric oxide synthase activity is a homeostatic adaptation to increased hemodynamic workload in hypertension and that this may help prevent end-organ damage. If these findings apply to humans, differences in end-organ disease seen in patients with similar degrees of hypertension may be due in part to genetic differences in vascular nitric oxide synthase activity in response to hypertension.
Key Words: nitric oxide • hypertension • angiotensin II • renal injury • left ventricular hypertrophy
Abbreviations: ACE = angiotensin-converting enzyme • Ang II = angiotensin II • DS = Dahl salt-sensitive • ET-1 = endothelin-1 • LVH = left ventricular hypertrophy • NO = nitric oxide • NOS = nitric oxide synthase • SHR = spontaneously hypertensive rats
This article has been cited by other articles:
 |
|
 |
|
  M. S. Joshi, C. Mineo, P. W. Shaul, and J. A. Bauer Biochemical consequences of the NOS3 Glu298Asp variation in human endothelium: altered caveolar localization and impaired response to shear FASEB J, September 1, 2007; 21(11): 2655 - 2663. [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. K. Johnson, W. Durante, K. J. Peyton, and R. A. Johnson Heme oxygenase-mediated endothelial dysfunction in DOCA-salt, but not in spontaneously hypertensive, rat arterioles Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1681 - H1687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Gnudi, G. Viberti, L. Raij, V. Rodriguez, D. Burt, P. Cortes, B. Hartley, S. Thomas, S. Maestrini, and G. Gruden GLUT-1 Overexpression: Link Between Hemodynamic and Metabolic Factors in Glomerular Injury? Hypertension, July 1, 2003; 42(1): 19 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Redon, M. R. Oliva, C. Tormos, V. Giner, J. Chaves, A. Iradi, and G. T. Saez Antioxidant Activities and Oxidative Stress Byproducts in Human Hypertension Hypertension, May 1, 2003; 41(5): 1096 - 1101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gschwend, H. Buikema, R. H. Henning, Y. M. Pinto, D. de Zeeuw, and W. H. van Gilst Endothelial dysfunction and infarct-size relate to impaired EDHF response in rat experimental chronic heart failure Eur J Heart Fail, March 1, 2003; 5(2): 147 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gschwend, H. Buikema, G. Navis, R. H. Henning, D. de Zeeuw, and R. P. E. van Dokkum Endothelial Dilatory Function Predicts Individual Susceptibility to Renal Damage in the 5/6 Nephrectomized Rat J. Am. Soc. Nephrol., December 1, 2002; 13(12): 2909 - 2915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Raij Workshop: Hypertension and Cardiovascular Risk Factors : Role of the Angiotensin II-Nitric Oxide Interaction Hypertension, February 1, 2001; 37(2): 767 - 773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wang, X. Yu, R. A. Cohen, and P. Brecher Distinct Effects of N-Acetylcysteine and Nitric Oxide on Angiotensin II-induced Epidermal Growth Factor Receptor Phosphorylation and Intracellular Ca2+ Levels J. Biol. Chem., April 14, 2000; 275(16): 12223 - 12230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Luke Hypertensive nephrosclerosis: pathogenesis and prevalence : Essential hypertension is an important cause of end-stage renal disease Nephrol. Dial. Transplant., October 1, 1999; 14(10): 2271 - 2278. [Full Text] [PDF]
|
|
|
|
|
|
F. C. Luft, E. Mervaala, D. N. Muller, V. Gross, F. Schmidt, J. K. Park, C. Schmitz, A. Lippoldt, V. Breu, R. Dechend, et al. Hypertension-Induced End-Organ Damage : A New Transgenic Approach to an Old Problem Hypertension, January 1, 1999; 33(1): 212 - 218. [Abstract] [Full Text] [PDF]
|
|