Role of platelets and leukocytes in modulation of vascular tone.

Abstract

Activated platelets and leukocytes release potent vasoactive factors that may modulate vascular tone. Activation of normal platelets produces dilatation of normal arteries. Vasodilatation is mediated by adenosine diphosphate (ADP), which releases endothelium-derived relaxing factor (EDRF) from endothelium. In atherosclerotic arteries, activation of platelets produces constriction and perhaps spasm. The constrictor response of atherosclerotic arteries is related in part to profound changes in vascular function: endothelial dysfunction with impaired endothelium-dependent vasodilator responses to ADP, and augmented vasoconstrictor responses to serotonin. In addition, hypercholesterolemia has a direct effect on platelets, resulting in impaired vasodilator responses. Thus, abnormal platelets and altered vascular function may both predispose to spasm of atherosclerotic arteries. Activation of leukocytes has little effect on resistance of large arteries in normal monkeys. In contrast, activation of leukocytes produces pronounced vasoconstriction in atherosclerotic monkeys. Possible mediators of vasoconstriction include prostaglandin E2, oxygen radicals, thromboxane, and a peptide (perhaps angiotensin II). In addition, leukocytes also alter vascular responses to platelets, in part by ADPase on the leukocyte membrane, which degrades ADP released by activated platelets. Leukocytes also release oxygen radicals, which may inactivate EDRF, thereby impairing ADP-mediated, endothelium-dependent vasodilator responses. Abnormal responses to platelets and leukocytes are largely reversed when atherosclerotic lesions regress in monkeys.