Protection of Endothelial Function: Targets for Nutritional and Pharmacological Interventions

Abstract: The vascular endothelium synthesizes and releases a spectrum of vasoactive substances and therefore plays a fundamental role in the basal and dynamic regulation of the circulation. Nitric oxide (NO)—originally described as endothe-lium-derived relaxing factor—is released from endothelial cells in response to shear stress produced by blood flow, and in response to activation of a variety of receptors. After diffusion from endothelial to vascular smooth muscle cells, NO increases intracellular cyclic guanosine-monophosphate concentrations by activation of the enzyme guanylate cyclase leading to relaxation of the smooth muscle cells. NO has also antithrombogenic, antiproliferative, leukocyte-adhesion inhibiting effects, and influences myocardial contractility. Endothelium-derived NO-mediated vascular relaxation is impaired in spontaneously hypertensive animals. NO decomposition by free oxyge