Blockade of histamine-mediated increases in microvascular permeability by H 1- and H 2-receptor antagonists

Abstract

The receptor mechanisms by which histamine increases microvascular fluid and protein efflux were studied in the canine forelimb perfused at constant flow. Skin lymph flow, protein concentration, and protein transport (flow × concentration) were examined during the intraarterial infusion of histamine alone and during the simultaneous infusion of histamine and the histamine antagonists tripelennamine or cimetidine. The infusion of histamine alone at 1.4 μg base/min resulted in a significant decrease in forelimb perfusion pressure and skin small-artery pressure and a small but significant increase in skin small-vein pressure. Histamine produced a 2 1 2 - fold increase in lymph flow, a 2-fold increase in lymph protein concentration, and a 5-fold increase in lymph protein transport. Infusion of this same dose of histamine during the simultaneous infusion of the H 1-receptor antagonist tripelennamine (10 μg/min) produced essentially the same changes in forelimb vascular pressures but failed to produce significant changes in lymph flow, lymph protein concentration, or lymph protein transport. Similarly, the infusion of cimetidine (250 μg/min), an H 2-receptor antagonist, concurrent with the infusion of histamine elicited no significant changes in lymph parameters but the fall in arterial pressures was attenuated. Since either an H 1- or an H 2-receptor antagonist is capable of blocking histamine-mediated increases in lymph flow and protein concentration, these data indicate a role for both H 1 and H 2 receptors in histamine-mediated increases in microvascular permeability.