title: Participation of vascular H1-receptors in histaminergic relaxation of rabbit middle cerebral artery in vitro.
abstract: 4-Methylhistamine relaxed potassium-constricted perfused rabbit middle cerebral arteries at low concentrations (3 X 10(-11) - 3 X 10(-8) M) and constricted them at high concentrations (3 X 10(-7) - 10(-4) M). The relaxation was antagonized by either cimetidine (3 X 10(-7) or 10(-6) M) or mepyramine (3 X 10(-8) M) given 20 min before testing a series of increasing concentrations of 4-methylhistamine, whereas the constriction was slightly potentiated by cimetidine and reversed by mepyramine. The reduction of relaxation was enhanced by a combination of both blockers. These results suggest the involvement of both H1- and H2-receptors in the 4-methylhistamine-induced relaxation. When dimaprit was compared with 4-methylhistamine, it acted only as a relaxing agent, not as a constricting agent. The dimaprit-induced relaxation was antagonized by either cimetidine (3 X 10(-7) M) or mepyramine (3 X 10(-8) M). The inhibition of relaxation was enhanced with a combination of both blockers. This supports the hypothesis that the dimaprit-induced relaxation in the rabbit cerebral artery is also mediated through both H1- and H2-receptors. The H1-agonists 2-methylhistamine and 2-pyridyl ethylamine induced two kinds of responses: an initial relaxation at low concentrations which was reversed by mepyramine (3 X 10(-8) or 10(-6) M) but not by cimetidine (10(-6) or 10(-5) M); this relaxation was followed at higher concentrations by a vasoconstriction which was antagonized by mepyramine (3 X 10(-8), 3 X 10(-7) or 10(-6) M) but not by cimetidine (10(-6) or 10(-5) M). Relaxation by these agents therefore seems to involve the participation of H1-receptors. The pharmacological effects of the histaminergic agonists and antagonists used could be explained by assuming that a distinction exists in the rabbit middle cerebral artery between the receptors concerned in H1-mediated relaxation and H1-mediated constriction.
mesh_terms: D000818:Animals; D002536:Cerebral Arteries / Q000502:physiology; D002927:Cimetidine / Q000494:pharmacology; D017259:Dimaprit; D004347:Drug Interactions; D006632:Histamine / Q000502:physiology*; D066298:In Vitro Techniques; D008761:Methylhistamines / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010627:Phenethylamines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011817:Rabbits; D011968:Receptors, Histamine / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000502:physiology*; D013890:Thiourea / Q000494:pharmacology
chemical_list: D008761:Methylhistamines; D010627:Phenethylamines; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; C029261:phenethylamine; C025566:4-methylhistamine; D002927:Cimetidine; D006632:Histamine; D013890:Thiourea; C026259:2-methylhistamine; D011738:Pyrilamine; D017259:Dimaprit