Participation of H₁-Receptors in Histamine-Induced Contraction and Relaxation of Horse Coronary Artery In Vitro

Abstract

The mechanisms of histamine-induced contraction and relaxation were investigated in rings isolated from a middle part of the left descending coronary arteries of horses. Intact and endothelium-denuded preparations were compared. Rings of horse coronary arteries contracted in response to histamine in a concentration dependent manner, but some of them relaxed with lower concentrations and contracted with higher concentrations. Removal of the endothelium abolished the relaxation and potentiated the contraction. The pD₂ values were 4.70±0.08 in the rings with intact endothelium and 4.95±0.08 in endothelium-denuded rings. Histamine-induced contractions in intact and denuded preparations were not affected by an H₂-antagonist, cimetidine, but were inhibited by an H₁-antagonist, diphenhydramine in non-competitive manner in the rings with endothelium and in competitive manner in denuded rings. After precontraction with PGF_SUP2α or norepinephrine, histamine relaxed preparations with intact endothelium (pD₂ value, 7.80±0.11), although histamine-induced relaxations were not observed in denuded preparations. The relaxation was competitively inhibited by diphenhydramine. Relaxing response was significantly attenuated by methylene blue, quinacrine, L-nitro-arginine, gossypol and AA861 but not by indomethacin. These results suggest that the hisidmine-induced contraction and relaxation in horse coronary arteries are mediated mainly by H₁-receptors in the smooth muscle and endothelium, respectively, and H₁-receptor activation of endothelial cells may liberate vasodilator substance(s).