Hypothermia-induced potentiation of histamine H2-receptor-mediated relaxation and cyclic AMP increase in the isolated mesenteric artery of the rabbit

Abstract

On helically cut strips of the rabbit's mesenteric artery, a temperature decrease from 42°C to 25°C reduced the contractile responses to histamine. Metiamide shifted the dose-response curve of the histamine-induced contraction towards higher values at 25°C, but not at 42°C. Furthermore, on arterial strips contracted by phenylephrine histamine evoked a dose-dependent relaxation at 25°C whereas at 42°C only slight relaxing responses to histamine occurred. Metiamide was capable of preventing the relaxation induced by histamine in a competitive manner. At 25°C the relaxation as produced by histamine was accompanied by increases in cyclic AMP which occurred prior to the relaxing effects. Metiamide abolished the cyclic AMP increase in response to histamine. At 42°C histamine was unable to elevate the cyclic AMP content. Thus, it is concluded that a cyclic AMP-mediated relexation due to stimulation of H₂-receptors counteracts the histamine-induced contraction and reduces the contractile responses to histamine at low temperatures. In addition, clear-cut evidence exists from the present study that also on artery smooth muscle the H₂-receptor-mediated responses are closely associated to cyclic AMP.