Analysis of vasoconstrictor responses to histamine in the hindlimb vascular bed of the rabbit

Hemodynamic responses to histamine were investigated in the anesthetized ra bbit. Intravenous injections of histamine induced dose-dependent decreases in systemic arterial pressure that were blocked by the H-1-receptor antagon ist pyrilamine but not the H-2 antagonist cimetidine. Injections of histami ne and the H-1 agonist 6-[2-(4-imidazolyl)ethylamine] -N-(4-trifuormethylph enyl)-heptanecardoxamide dimaleate (HTMT) into the hindlimb perfusion circu it increased hindlimb perfusion pressure, whereas the H-2 agonist dimaprit decreased perfusion pressure and the H-3-receptor agonist R-(-)-alpha-methy lhistamine did not alter perfusion pressure. Pyrilamine reduced hindlimb va soconstrictor responses to histamine and HTMT but did not alter vasodilator responses to dimaprit. Cimetidine reduced the response to dimaprit but did not alter vasoconstrictor responses to histamine or HTMT. The H-3-receptor antagonist thioperamide was without effect on responses to the histamine a gonists. These data suggest the presence of H-1 and H-2 receptors and that histamine for the most part acts by stimulating H-1 receptors to produce va soconstriction in the hindlimb vascular bed of the rabbit. Responses to his tamine, HTMT and norepinephrine were significantly enhanced by a nitric oxi de synthase inhibitor at a time when vasodilator responses to dimaprit were unaltered and responses to acetylcholine were significantly reduced. Respo nses to histamine and the H-1 and H-2 agonists were not affected by the cyc looxygenase inhibitor meclofenamate or by ATP-sensitive K+ channel, alpha-a drenergic, or angiotensin AT(1) receptor antagonists. The present data sugg est that H-1 receptors mediate both systemic vasodepressor and hindlimb vas oconstrictor responses to histamine.