Mechanisms of histamine-induced relaxation in isolated monkey and dog coronary arteries.
Relaxations induced by histamine in helical strips of monkey coronary arteries were attenuated either by chlorpheniramine or cimetidine; the H1 antagonist suppressed the fast component of relaxation, whereas the H2 antagonist reduced the slow component. Combined treatment with these antagonists abolished the amine-induced relaxation. The relaxation was not influenced by indomethacin; however, the fast component of relaxation was inhibited by 5, 8, 11, 14-eicosatetraynoic acid, AA861, a lipoxygenase inhibitor, and methylene blue. In the arteries treated with methylene blue, relaxations were abolished by cimetidine. Removal of the endothelium reduced the relaxation markedly or reversed the relaxation to a contraction; chlorpheniramine reversed the contraction to a relaxation. In dog coronary arterial strips, histamine-induced relaxations were not attenuated by removal of the endothelium. Cimetidine shifted the dose-response curve for histamine to the right, but chlorpheniramine did not alter the response. Indomethacin, AA861 and methylene blue failed to inhibit the relaxation. The response of monkey coronary arteries to histamine appears to be a sum of the slight, persistent contraction, the transient relaxation and the slowly developing relaxation. The transient relaxation may be mediated by H1 receptors in the endothelium, the activation of which yields relaxing factor, resulting in an increase of cellular cyclic GMP in smooth muscle. The contraction and the slow relaxation appear to be associated with H1 and H2 receptors, respectively, in smooth muscle cells. Dog coronary arterial relaxations induced by histamine may be mediated exclusively by H2 receptors in muscle cell membrane.
D000818:Animals; D016227:Benzoquinones; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008251:Macaca; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D011809:Quinones / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D016227:Benzoquinones; D011809:Quinones; D002744:Chlorpheniramine; D002927:Cimetidine; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D006632:Histamine; D008751:Methylene Blue; D007213:Indomethacin