Histamine receptors in peripheral vascular beds in the cat.

1. The vasodilator activity of histamine has been studied in anaesthetized cats. 2. Histamine causes dose-dependent vasodilatation in the vasculature of the hind-limb and mesentery, perfused with blood at constant flow. 3. Experiments using the selective antagonists mepyramine and metiamide indicate the involvement of both H1- and H2-receptors in the vasodilator responses to histamine. Mepyramine (2.5 X 10(-6) mol/kg), causes displacement of the histamine dose-response curve. This displacement is maximum with a dose-ratio of about 10. Further dose-dependent displacement of the dose-response curve occurred after metiamide (4 X 10(-7) mol kg-1 min-1 and 2 X 10(-6) mol kg-1 min-1), although these doses of metiamide had no effect on histamine responses in the absence of mepyramine. 4. Vasodilator responses could also be elicited by the selective H1-receptor agonists, 2-methylhistamine, 2-(2-aminoethyl)pyridine and 2-(2-aminoethyl)thiazole and the selective H2-receptor agonist, 4-methylhistamine. 5. The selectivity of mepyramine and metiamide as histamine receptor antagonists was confirmed by their failure to reduce the vasodilator responses to acetylcholine, isoprenaline and bradykinin.