Role of serotonin, histamine, and thromboxane A2 in platelet-induced contractions of coronary arteries and aortae from rabbits.

The present study was undertaken to clarify the underlying mechanisms responsible for contractions of isolated coronary arteries and aortae from rabbits in response to thrombin-stimulated autologous platelets. Thrombin-stimulated platelets evoked potent contractions of both arteries in a platelet concentration-related manner. Pretreatment of platelets with aspirin, which almost completely inhibited thromboxane A2 synthesis but not the release reaction of biologic monoamines from platelets, caused only slight suppression of platelet-induced contractions of both arteries. Ketanserin as well as methysergide markedly inhibited aortic contractions to platelets. In contrast, the contractile responses of coronary arteries to platelets were suppressed by methysergide but not by ketanserin. Pretreatment of the arteries with diphenhydramine did not inhibit the aortic responses to platelets, but significantly suppressed coronary arterial contractions induced by higher concentrations of platelets. Phentolamine had no inhibitory effects on the responses of either artery to platelets. Pretreatment of arteries with aspirin did not affect the contractile responses of either artery to platelets. The contractile responses of aortae to exogenously administered serotonin were competitively antagonized by ketanserin, but those of coronary arteries were not. Coronary contractions to serotonin were competitively inhibited by methiothepin and significantly suppressed by methysergide. The contractile responses of both arteries to histamine were antagonized by diphenhydramine but not by cimetidine. On the basis of our results obtained from studies in organ chamber, we conclude that a major role of thromboxane A2 was not demonstrated in platelet-induced contractions of the arteries, and that those of aortae were mainly mediated by platelet-derived serotonin at S2 receptor and those of coronary arteries at S1-like receptor. The contractions of coronary arteries in responses to higher concentrations of platelets were partly mediated by histamine at H1 receptor.