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 dose-dependent 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-pretreated 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.