CHARACTERISTICS OF VASODILATATION INDUCED BY ACETYLCHOLINE AND PLATELET-ACTIVATING-FACTOR IN THE RAT MESENTERIC ARTERIAL BED

We examined the nature of the endothelium-dependent vasodilator effect s of acetylcholine and platelet-activating factor (PAF) on the perfuse d mesenteric arterial bed of the rat. Acetylcholine-induced concentrat ion-dependent vasodilatation of the mesentery was not affected by pret reatment with 10(-4) M N-G-monomethyl-L-arginine (L-NMMA), indomethaci n, ouabain, or glibenclamide, whereas pretreatment with 10(-5) M oxyhe moglobin, 10(-5) M methylene blue, or 10 mM tetraethylammonium shifted the concentration-response curves to the right. PAF-induced concentra tion-dependent vasodilatation of the mesentery was inhibited by pretre atment with L-NMMA, oxyhemoglobin, or methylene blue, and slightly but significantly inhibited by tetraethylammonium, whereas indomethacin, glibenclamide, and ouabain had no inhibitory effects. PAF-induced vaso dilatation of the mesentery was more sensitive to nitric oxide-cyclic GMP pathway inhibitors (a combined application of L-NMMA, oxyhemoglobi n, and methylene blue) than was the vasodilatation induced by acetylch oline. Perfusion of the mesentery preparations with acetylcholine or P AF increased the levels of cyclic GMP in the effluent. These effects w ere completely inhibited by L-NMMA or oxyhemoglobin. These results sug gest that the endothelium-dependent vasodilator effects of PAF are pri marily mediated by endothelium-derived nitric oxide (NO) and those of acetylcholine are mediated by both NO and endothelium-derived hyperpol arizing factor (EDHF).