Involvement of platelet-activating factor in endothelin-induced vascular smooth muscle cell contraction

This study was designed to elucidate the participation of platelet-activating factor (PAF) in Endothelin-Induced vascular constriction in vivo and in vitro. The microvascular hemodynamic changes in rat mesentery induced by the superfusion of endothelin-1 (ET-1) were visualized through an intravital microscopic system. It was revealed in vivo that ET-1 in a range of 100 fM-10 pM caused a sustained arteriolar constriction in a dosedependent manner. Pretreatment with CV-6209, a selective PAF antagonist, significantly attenuated the constrictive change in arterioles. Changes of intracellular Ca²⁺mobilization after treatment with ET-1 were investigated in vitro using a cell line (A-10 cell) derived from rat arterial smooth muscle cells. ET-1 caused a prompt rise in the fura-2-associated fluorescence intensity in the individual A-10 cell and it fell to a lower plateau level that was still higher than the baseline value. CV-6209-pre-treated cells did not show the rapid-phase mobilization of Ca²⁺, but showed the slow late phase of Ca²⁺activation. The present study demonstrates that PAF may be involved in Endothelin-Induced microvascular constriction by mediating the mobilization of Ca²⁺in vascular smooth muscle cells.