Effect of histamine and 1,4-methylhistamine on gastric vascular resistance in dogs

The goal of this study was to compare the relative potency of histamine and its metabolite, 1,4-methylhistamine, as vasodilators of the gastric circulation. Changes in vascular resistance were measured during local intra-arterial infusion of graded doses of histamine and 1,4-methylhistamine to an ex vivo segment of dog stomach. Infusate concentrations were adjusted to deliver calculated arterial blood concentrations of 0, 3.7, 11, 33, 100, 300, and 900 ng/ml of each substance to the stomach segment. We found that histamine caused rapid dose-related decreases in gastric vascular resistance of up to -47.6 +/- 1.3% compared with control values. The effects of histamine were reversible when infusions ended. In contrast, there were no statistically significant changes in vascular resistance at any dose of 1,4-methylhistamine. In addition, modifications to previous methods using histamine antagonists resulted in greater attenuation of histamine-induced gastric vasodilation. Our results support a role for locally released histamine, but not for 1,4-methylhistamine, as a mediator of gastric vasodilation.