Monoxyde d'azote et hypertension artérielle

Abstract

The relaxing endothelial function, dependent on NO-synthase activity and cyclic GMP production, plays a tonic role in the regulation of arterial vasomotricity. The endothelial NO-synthase activity is dependent on endothelial cell calcium. In vitro, vasoactive substances, such as acetylcholine and bradykinin, exert their relaxing action on smooth muscle cells by increasing calcium in endothelial cells. In vivo, the basal NO-synthase activity is under the control of the shear stress exerted by blood on the endothelial surface. Acute or chronic blockade of NO-synthase activity with L-arginine antagonists is associated with a rise in pressure and a fall in flow. The renal vascular bed is particularly sensitive to NO-synthase blockade. In primary, essential hypertension, mimicked by the spontaneously hypertensive rat, the vasorelaxing NO-synthase activity appears to be normal. In contrast, sodium overload is associated with an overactivity of the NO-synthase. A defect in this counter- regulation may participate in some models of essential hypertension depending on salt overload, such as the experimental model of salt sensitive Dahl rat. Shear stress depends on blood flow velocity and on the dimension of the arterial lumen and is not directly dependent on pressure. Pathophysiological situations associated with chronic changes in blood flow, such as arteriovenous fistula, are associated with chronic modifications of shear stress and endothelial relaxing function, leading to modifications of arterial wall structure. Congestive heart failure is an example of a possible chronic decrease in shear stress leading to a decrease in the endothelial relaxing function. The arterial lumen widening could be involved in the diminished endothelium-derived relaxing factor activity observed with aging.