Histamine H1-receptors mediate endothelium-dependent relaxation of rat isolated pulmonary arteries.
Histamine has been reported to cause endothelium-dependent relaxation of vascular smooth muscle and vasodilation. This study was undertaken to examine the inhibitory effects of histamine on cylindrical segments of extrapulmonary arteries isolated from male Sprague Dawley rats. In arterial segments precontracted with phenylephrine (10 microM), histamine (0.1-100 microM) elicited concentration-dependent relaxation responses. Removal of the endothelium or pretreatment with methylene blue (10 microM) abolished relaxation responses to low concentrations of histamine and markedly inhibited those caused by histamine at concentrations greater than 1 microM. Incubation of endothelium-intact arterial segments with pyrilamine (1 microM) caused a significant rightward shift of the histamine concentration-response curves. Treatment of the segments with cimetidine (100 microM) or indomethacin (10 microM) only minimally antagonized histamine-induced relaxation in arteries with endothelium. Residual relaxation responses observed in arteries stripped of endothelium were unaffected by pretreatment with cimetidine, indomethacin, or pyrilamine. The results suggest that the inhibitory effect of histamine in rat pulmonary arteries is mediated predominantly by activation of H1-receptors on the endothelium and the subsequent release of endothelium-derived relaxing factor(s).
Szarek
J L
JL
Department of Pharmacology, Marshall University School of Medicine, Huntington, West Virginia 25755-9310.
Bailly
D A
DA
Stewart
N L
NL
Gruetter
C A
CA
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*
D011969:Receptors, Histamine H1; D010656:Phenylephrine; D009569:Nitric Oxide; D002927:Cimetidine; D006632:Histamine; D011738:Pyrilamine; D007213:Indomethacin