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.
Kurose
I
I
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Miura
S
S
Suematsu
M
M
Fukumura
D
D
Nagata
H
H
Sekizuka
E
E
Tsuchiya
M
M
D000818:Animals; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D016232:Endothelins / Q000494:pharmacology*; D016257:Fura-2; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209; D002118:Calcium; D016257:Fura-2