VERAPAMIL AND ASPIRIN MODULATE PLATELET-MEDIATED VASOMOTION IN ARTERIAL SEGMENTS WITH INTACT OR DISRUPTED ENDOTHELIUM

Objectives. This study was designed to examine the effects of verapami l and aspirin, which decrease thromboxane A2 and serotonin release, on the modulation of vascular tone by platelets. Background. Aggregating platelets cause constriction of de-endothelialized arterial segments through thromboxane A2 and serotonin release. These cells cause relaxa tion of arterial segments with intact endothelium through release of t he endothelium-derived relaxing factor. Methods. Healthy subjects were given either no drug, verapamil or aspirin for greater-than-or-equal- to 5 days before their platelets were obtained. The effects of platele ts obtained from subjects before and after treatment with aspirin or v erapamil on the tone of rat aortic rings were determined. Results. As expected, control platelets (before verapamil or aspirin treatment) in duced concentration-dependent relaxation of rat aortic rings with inta ct endothelium and a concentration-dependent contraction of de-endothe lialized rings. Verapamil treatment enhanced (p < 0.02) the platelet-m ediated relaxation in rings with intact endothelium and abolished plat elet-mediated constriction (p < 0.01) in the de-endothelialized rings. Aspirin treatment also abolished (p < 0.05) platelet-mediated constri ction of the de-endothelialized rings. The de-endothelialized rings co ntracted normally in response to the synthetic thromboxane A2 analogue U46,619, as well as to serotonin, indicating that the vascular smooth muscle response to thromboxane A2 and serotonin was intact. Conclusio ns. This study provides evidence for the modulation of platelet-mediat ed vasoconstriction of de-endothelialized arterial segments by prior t reatment of subjects with verapamil or aspirin. In clinical syndromes characterized by endothelial dysfunction or disruption, treatment with verapamil or aspirin may modify platelet-vessel wall interactions.