Characteristics of H2-receptor blockade in the canine mesenteric circulation.

Studies were conducted in anesthetized dogs to determine the effect of metiamide, an H₂-receptor antagonist to histamine, on the mesenteric vasodilatory response to histamine. Histamine alone (0.5 μg/kg-min) elicited a vasodilator response from the superior mesenteric artery consisting of two components: an early transient spike phase followed by a later stable and more sustained dilation of lesser amplitude. Metiamide, a dose-related manner, inhibited this late stable dilatory response and completely abolished it at a dose of 10^?4 mole/min. Histamine, on the other hand, in a dose of 1.25 μg/kg-min, overcame the inhibitory response to metiamide. These findings suggest that the mesenteric vasodilatory response to histamine is mediated through at least two distinct receptors. The ability of metiamide to inhibit the late stable vasodilation in a dose-related and surmountable fashion supports the hypothesis that this late phase is mediated predominantly through H₂ receptors and that the mechanism of blockade involves competitive inhibition.