thiourea and phenethylamine

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.

Topics: Animals; Cerebral Arteries; Cimetidine; Dimaprit; Drug Interactions; Histamine; In Vitro Techniques; Methylhistamines; Muscle Relaxation; Muscle, Smooth, Vascular; Phenethylamines; Pyrilamine; Rabbits; Receptors, Histamine; Receptors, Histamine H1; Thiourea

The effects of selective histamine receptor stimulation on relaxation to norepinephrine (NE) were determined in four sizes of spirally cut porcine coronary arteries. The four sizes of porcine coronary artery were designated very large (greater than 4.0 mm o.d.), large (1.5-2.5 mm o.d.), medium (0.8-1.2 mm o.d.), and small (less than or equal to 0.5 mm o.d.). Histamine, dimaprit, 2-pyridylethylamine, and histamine plus either mepyramine or metiamide did not alter the concentration-response curve to NE. Thus histamine receptor stimulation does not change relaxations of porcine coronary arteries to NE.

Topics: Animals; Coronary Vessels; Dimaprit; Histamine; In Vitro Techniques; Muscle Relaxation; Muscle, Smooth, Vascular; Myocardial Contraction; Norepinephrine; Phenethylamines; Receptors, Histamine; Swine; Thiourea