CHEMICALLY-INDUCED PLATELET LYSIS CAUSES VASOCONSTRICTION BY RELEASE OF SEROTONIN

Our previous studies have shown that menadione is cytotoxic to platele ts, leading to substantial release of vasoactive substances. To test w hether platelet lysis induced by menadione could cause vasoconstrictio n, we investigated the effect of platelet lysate induced by menadione on rat aorta in organ bath system. We showed that menadione-induced pl atelet lysate caused vasoconstriction in a dose-and time-dependent man ner. These effects were seen in aortic rings both with and without end othelium, but it was much greater in rings without intact endothelium. The time course of vasoconstriction was well correlated with the time courses of platelet lysis (assessed by lactate dehydrogenase release) as well as serotonin release. The vasoconstriction by platelet lysate was blocked by serotonin antagonists, ketanserin, and LY53,857, but n ot by thromboxane A(2) (TXA(2)) receptor antagonist, SQ29,548, suggest ing that vasoconstriction mainly occurred secondary to the release of serotonin in our in vitro system. However, potentiation of vasoconstri ction by combined treatment of serotonin and a stable TXA(2) mimic, U4 6619, suggests the possibility of the increased risk for vasoconstrict ion in vivo. In addition, the serotonin-induced vasoconstriction was p otentiated by residual menadione present in the organ bath. These resu lts suggest that chemically induced platelet cytotoxicity can provoke alteration in vasomotor tone by release of serotonin. (C) 1998 Academi c Press.