Interaction between histamine and nitric oxide in rat mast cells and in isolated guinea pig hearts.

BACKGROUND: Histamine and nitric oxide (NO) are present in guinea pig hearts and in rat mast cells (MCs) of the serosal phenotype. Histamine and NO are simultaneously released upon immunological challenge of isolated hearts of actively sensitised guinea pigs. MCs release histamine in response to antigen and NO in response to stirring. This has prompted us to study the interaction between histamine and NO in rat MCs and in guinea pig hearts. METHODS: The experiments have been carried out in isolated purified rat serosal MCs and in isolated perfused guinea pig hearts. The generation of NO by both preparations has been evaluated as nitrites (NO2-) by means of the Griess reaction. RESULTS: Histamine upregulates the generation of NO both in rat MCs and in guinea pig hearts. The effect is abolished by blocking NO synthase and preferentially mimicked by a selective H2-receptor agonist. A selective H3-receptor agonist downregulates the generation of NO in lipopolysaccharide-pretreated MCs and in bradykinin-pretreated guinea pig hearts. CONCLUSION: A mutual relationship between histamine and NO in allergic inflammation could be envisaged.