The L-arginine-nitric oxide pathway in hypertension.

Nitric oxide is involved in the regulation of resting vascular tone, adaptation of blood flow to metabolic demand of tissue, and adaptation of vessel diameter to volume of inflow, ie, flow-mediated dilation. Arterial hypertension is associated with an increased vascular tone of resistance vessels, a reduced compliance of conduit arteries, along with a thickening of the intima-media leading to vascular remodeling. Dysfunctional endothelium triggers such maladaptive processes. A reduced bioavailability of nitric oxide has been shown in hypertensive individuals dependent on the duration and severity of arterial hypertension. Angiotensin-converting enzyme inhibitors reverse endothelial dysfunction, whereas a concomitant reduction in significant cardiac events due to improved bioavailability has yet to be established. Long-term follow-up studies in individuals with manifest endothelial dysfunction and in offspring from hypertensive patients underscore the prognostic and genetic significance of a reduced nitric oxide bioavailability for the pathophysiology of arterial hypertension.