NITRIC-OXIDE IN HYPERTENSION - RELATIONSHIP WITH RENAL INJURY AND LEFT-VENTRICULAR HYPERTROPHY

Hypertension is accompanied by architectural changes in the kidney, he art, and vessels that are often maladaptive and can eventually contrib ute to end-organ disease such as renal failure, heart failure, and cor onary disease. Nitric oxide, an endogenous vasodilator and antithrombo tic agent synthesized in the endothelium by a constitutive nitric oxid e synthase, inhibits growth-related responses to injury in vascular ce lls. Specifically, in the presence of hypertension, nitric oxide may w ork in the kidney by inhibiting both mesangial cell hypertrophy and hy perplasia as well as synthesis of extracellular matrix and in the hear t and systemic vessels by modulating smooth muscle cell hypertrophy an d hyperplasia. The effects of nitric oxide are antagonistic of the eff ects of angiotensin II. Shear stress and cyclic strain, physical force s known to operate in hypertension, are accompanied by increases in en dothelial nitric oxide synthase expression, nitric oxide synthase prot ein, and nitric oxide synthase activity in endothelial cells. Experime ntal studies using genetic models of hypertension show a variation in hypertension-modulated vascular nitric oxide synthase activity in diff erent strains of rats. These studies suggest that upregulation of vasc ular nitric oxide synthase activity is a homeostatic adaptation to inc reased hemodynamic workload in hypertension and that this may help pre vent end-organ damage. If these findings apply to humans, differences in end-organ disease seen in patients with similar degrees of hyperten sion may be due in part to genetic differences in vascular nitric oxid e synthase activity in response to hypertension.