Nitric oxide, oxidative stress and vascular endothelium in health and hypertension.

Oxidative stress contributes to homeostasis in vascular cells. However, excessive ROS is pathophysiological and contributes to impaired endothelium-dependent dilation in hypertension by decreasing NO bio-availability. NADPH oxidase is upregulated in hypertension by humoral and mechanical signals, and quantitatively this enzyme makes the largest contribution to ROS production. Genetic and chemical manipulation of NADPH oxidase and of antioxidant enzymes cause predictable changes in oxidative stress and endothelium-dependent function in hypertension. The chemical antioxidant glutathione also impacts endothelium-mediated vascular function, possibly through maintenance of S-nitrosothiols and via other independent antioxidant effects. The effects of changes in thiols and nitrosothiols on vasomotor function in hypertension need to be examined. H(2)O(2) is believed to act as an EDHF physiologically. Thus, there must be competition between the influence of ROS and oxidative stress on NO-dependent dilation versus EDHF-dependent dilation. The crossover effects of ROS on the three main endothelium-dependent dilatory pathways must be examined in hypertension models.