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Characterization of histamine receptors in cat cerebral arteries in vitro and in situ

L Edvinsson, PM Gross and A Mohamed

Histamine is probably a mediator of vascular responses in the brain, but there is little experimental evidence for its importance in this role. By using both in vitro and in situ techniques, we have studied responses of cat pial arteries to stimulation of histamine receptors by pharmacological agents. In vitro, histamine and 2,2-pyridylethylamine (PEA, H1 agonist) caused contraction of resting arteries while impromidine (H2 agonist) was without effect. The PEA-induced constriction was blocked by the histamine H1 antagonist, mepyramine. When the arteries were precontracted (by 3 X 10(-6) M prostaglandin F2 alpha), however, all three agents caused vascular relaxation with an order of effectiveness as follows: histamine = impromidine much much greater than PEA. The responses of histamine and impromidine were reduced by the H2-antagonists, metiamide or cimetidine. Schild plots for the H2 receptor antagonists resulted in pA2 values of 6.90 and 7.03 for metiamide and cimetidine, respectively. In situ, neither agonist caused pial arterial constriction. Impromidine was considerably more effective than PEA in producing arterial dilatation. Metiamide reduced the effect of impromidine, whereas the dilatation of PEA was reduced by mepyramine. Dilatations resulting from PEA persisted in the presence of metiamide. Our results are consistent with the hypothesis that histamine H2 receptors are present in cerebral vascular smooth muscle as identified both in vitro and in situ. Indications for the additional presence of H1 receptors are, however, weak.

Volume 225, Issue 1, pp. 168-175, 04/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1983 by the American Society for Pharmacology and Experimental Therapeutics.