Nitric oxide (NO) is an endogenous vasodilator and antithrombogenic agent synthesized in the endothelium by a constitutive NO synthase (NOS). In addition, NO is a powerful endogenous inhibitor of growth-related responses in vascular cells and thereby participates in vascular remodeling in response to injury. In the kidney, NO inhibits mesangial cell hypertrophy and hyperplasia as well as mesangial cell synthesis of extracellular matrix. In the heart and systemic vessels, NO modulates vascular smooth muscle cell hypertrophy as well as hyperplasia. In endothelial cells, shear stress and cyclic strain, physical forces known to be operative during hypertensive states, induce a parallel increase in endothelial NOS expression, NOS protein, and NOS activity. Recent studies in animals suggest that in hypertension the physiological adaptation to the increased hemodynamic workload is the upregulation of vascular NOS activity. Moreover, upregulation of NOS activity may contribute to forestalling end-organ complications of hypertension, namely renal failure, left ventricular hypertrophy, coronary artery disease, and stroke. Conversely, failiure to augment, or an actual decrease in vascular NOS activity, increases the susceptibility of end-organs to hypertensive injury. Studies in genetic models of hypertension in rats support this contention and suggest that vascular NOS activity in response to hypertension may be genetically determined and varies in different strains of rats. On the basis of these studies in animals and preliminary studies in humans we speculate that genetically conditioned heterogeneity in vascular NOS activity in response to hypertension may explain, at least in part, the differences in end-organ disease observed clinically in individuals with hypertension of similar severity.
|Original language||English (US)|
|Journal||Journal of Hypertension, Supplement|
|State||Published - Dec 1 1998|
- Angiotensin II
- Nitric oxide
ASJC Scopus subject areas
- Internal Medicine