Reactive oxygen species and the control of vasomotor tone

During the past 15 years it has become clear that nitric oxide (NO(*)) released by endothelial cells plays a crucial role in vascular homeostasis. In addition to its role as a vasodilator, NO(*) inhibits platelet aggregation and smooth muscle proliferation and decreases the expression of proinflammatory molecules by the endothelium. Importantly, the activity of the NO system is reduced in a variety of pathophysiologic condition, including atherosclerosis, hypercholesterolemia, hypertension, diabetes, cigarette smoking, and aging. The mechanisms whereby these various conditions alter endothelium-dependent vascular relaxation are likely multifactorial. Several lines of evidence have suggested that oxidative inactivation of nitric oxide is likely important in some of these conditions. These studies have shown that in the vessel, a tenuous balance exists between the steady state levels of nitric oxide and the superoxide anion (O2(-*)). In this review, the factors that seem to modulate vascular levels of superoxide anion and nitric oxide will be discussed and evidence that imbalances between these two can predispose to alterations of vascular regulation will be presented.