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The effects of histamine and 4-methylhistamine (a selective H₂-agonist) were studied on the isolated rat stomach fundus and rabbit aortic strips superfused with Krebs’ solution. The contraction induced by histamine was found to be mediated via mepyramine-sensitive H₁, while the relaxation induced by the amine through metiamide-sensitive H₂-receptors in both smooth muscles. Prior addition of metiamide to the superfusion medium caused an apparent dose-related potentiation in the response to histamine on the aortic strip but not on the stomach fundus strip. The relaxation produced by histamine on the aortic strip demonstrated when the muscle was pretreated with mepyramine and contracted by angiotensin II or serotonin. Metiamide competitively inhibited the relaxation induced by histamine but not by papaverine in both smooth muscles. 4-Methylhistamine produced only a relaxation in the rat stomach fundus which could be competitively inhibited by metiamide. This analog had no agonistic property in the aortic strip. From these results it was concluded that histamine H₁- and H₂-receptors are present in both smooth muscles. The predominant contractile effect of histamine is mediated through H₁-receptors and the relaxing effect of the amine through H₂-receptors.

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Contribution of endothelial cells (ECs) to the effects of histamine (HA) was investigated on the isolated guinea-pig main pulmonary artery (GPPA) strips precontracted with noradrenaline (NA). HA caused dose-dependent relaxation at the concentrations ranged between 10(-8) to 10(-6) M but produced a contraction when a relatively higher concentration (10(-5) M) was used in unrubbed strips. Cimetidine partially inhibited the relaxing effect of HA without altering its constrictive action. In rubbed strips, however, HA produced a dose-dependent contraction. The constrictive effect of HA in rubbed strips enhanced after addition of cimetidine to the incubation medium. HA elicited a concentration-dependent relaxation in both unrubbed and rubbed strips in the presence of mepyramine. Impromidine produced a relaxation in the strips with and without endothelium. These data was taken as an evidence indicating that HA caused a relaxation in the isolated GPPA strips, first causing the release of endothelium derived relaxing factor (EDRF) which is triggered by H1-receptors and secondly by the direct stimulation of H2-receptors.