Endothelium-dependent relaxant action of platelet activating factor in the rat mesenteric artery.

Vasorelaxant action of platelet activating factor (PAF) was examined in perfused mesenteric vascular beds and mesenteric artery strips isolated from rats. PAF caused a dose-dependent vasodilation of norepinephrine-contracted mesenteric vascular bed, which was sensitive to CV-3988, a PAF antagonist, but insensitive to tetrodotoxin, atropine, propranolol and indomethacin. PAF also caused a relaxation of phenylephrine-contracted mesenteric artery strips at above 3 X 10(-12) M. Much higher concentrations of PAF were required to relax the aorta, carotid and pulmonary arteries. The PAF- and acetylcholine (ACh)-induced relaxations of mesenteric artery were dependent on the presence of endothelium and were inhibited by either hydroquinone and methylene blue, which inhibit the action of endothelium-derived relaxing factor (EDRF), or L-canavanine, which inhibits the formation of nitric oxide from L-arginine. Phospholipase A2 inhibitors such as quinacrine and ONO-RS-082 abolished the relaxation induced by ACh but did not affect that by PAF. Thus, PAF induces a vasorelaxation by releasing EDRF from endothelial cells as ACh does, although the pathway to produce the substances by PAF may be different from that by ACh.