Histamine-induced venodilation in human beings involves both H1 and H2 receptor subtypes.

Histamine is a potent vasodilatory substance released during anaphylaxis. The purpose of this study was to investigate the mechanism by which histamine produces venodilation in humans in vivo with the use of the dorsal hand-vein compliance technique. In healthy volunteers full dose-response curves were constructed by infusing histamine, before and after administration of an H1 or H2 antagonist or both antagonists, into dorsal hand veins preconstricted with the alpha-adrenergic agonist phenylephrine. In the presence of the H1 antagonist brompheniramine (530 ng/min), the maximal venodilatory response to histamine decreased from 128% +/- 57% to 78% +/- 15% (p < 0.05). In the presence of H2 antagonist cimetidine (49 micrograms/min), the maximal venodilatory response to histamine decreased from 120% +/- 33% to 48% +/- 26% (p < 0.01). Concurrent infusion of histamine with the combination of cimetidine and diphenhydramine resulted in almost complete abolishment of histamine-induced venodilation. Methylene blue (6.8 micrograms/min), an inhibitor of the action of endothelium-derived relaxing factor, decreased the vasodilatory response to histamine from 131% +/- 23% to 73% +/- 24% (p = 0.01). The results suggest that the venodilatory response of histamine is mediated through both H1 and H2 receptor subtypes and that this response is mediated in part by endothelium-derived relaxing factor.