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 effects of acetylcholine and platelet-activating factor (PAF) on the perfused mesenteric arterial bed of the rat. Acetylcholine-induced concentration-dependent vasodilatation of the mesentery was not affected by pretreatment with 10(-4) M NG-monomethyl-L-arginine (L-NMMA), indomethacin, ouabain, or glibenclamide, whereas pretreatment with 10(-5) M oxyhemoglobin, 10(-5) M methylene blue, or 10 mM tetraethylammonium shifted the concentration-response curves to the right. PAF-induced concentration-dependent vasodilatation of the mesentery was inhibited by pretreatment 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 vasodilatation of the mesentery was more sensitive to nitric oxide-cyclic GMP pathway inhibitors (a combined application of L-NMMA, oxyhemoglobin, and methylene blue) than was the vasodilatation induced by acetylcholine. Perfusion of the mesentery preparations with acetylcholine or PAF increased the levels of cyclic GMP in the effluent. These effects were completely inhibited by L-NMMA or oxyhemoglobin. These results suggest that the endothelium-dependent vasodilator effects of PAF are primarily mediated by endothelium-derived nitric oxide (NO) and those of acetylcholine are mediated by both NO and endothelium-derived hyperpolarizing factor (EDHF).
Kamata
K
K
Department of Physiology and Morphology, Hoshi University, Tokyo, Japan.
Numazawa
T
T
Kasuya
Y
Y
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D010972:Platelet Activating Factor; D010042:Ouabain; D000109:Acetylcholine