Introduction

The vascular endothelium is a dynamic cellular interface between the blood and subendothelial tissue and is critical for the maintenance of blood flow and hemostasis. The endothelium releases substances (Fig. 29.1) that play an important role in the modulation of vascular tone and permeability, as well as blood fluidity. These substances affect vascular tone by causing both vasodilation [prostaglandin I2 (PGI2), nitric oxide (NO), and endothelium- derived hyperpolarizing factor (EDHF)] and vasoconstriction [thromboxane A2 (TXA2) and endothelin (Et-1)], with the interaction between these two processes ultimately determining the tone of the vessel. In addition to modulating vascular tone, substances released from the endothelium affect platelet adhesion and aggregation. Nitric oxide inhibits platelets adhesion and aggregation, and PGI2 inhibits platelet aggregation.

Abnormal endothelial responses (endothelial dysfunction) or frank damage to or denudation of the endothelium promotes a prothrombotic state by reducing antiplatelet factors and by inducing adhesion molecule expression. Furthermore, endothelial dysfunction may be involved in the pathogenesis of several cardiovascular disorders, including atherosclerosis, diabetes mellitus, essential hypertension, hypercholesterolemia, and hyperhomocysteinemia.

In this chapter we will review the control of normal endothelial function, with specific emphasis on antiplatelet effects of substances released from the endothelial cell. We will also review the consequences of endothelial dysfunction, giving specific examples in several disease states.