MECHANISMS INVOLVED IN THE VASORELAXING INFLUENCE OF HISTAMINE ON ISOLATED HUMAN SUBCUTANEOUS RESISTANCE ARTERIES

The effects of histamine were analysed on human subcutaneous small art eries. No effect was seen on non-precontracted preparations. After pre contraction (norepinephrine 1 mu M and K+ 30 mM) histamine potently re laxed the arteries (EC50 = 0.3 mu M; max. effect = 95% relaxation). Th e histamine H-1 receptor antagonist, pyrilamine (10 mu M), had only a small, non-significant inhibitory influence on histamine-induced relax ation while the histamine H-2 receptor antagonist, cimetidine (0.1 mM) , had a significant inhibitory influence. Relaxation was completely bl ocked in the presence of both antagonists. Both 2-pyridylethylamine (h istamine H-1 receptor agonist) and dimaprit (histamine H-2 receptor ag onist) elicited relaxation. Removal of endothelium reduced the relaxat ion effects of histamine and 2-pyridylethylamine, but not of dimaprit. Inhibition of nitric oxide synthesis by nitro-L-arginine significantl y inhibited histamine-induced relaxation and even more clearly the cim etidine-resistant component. We conclude that histamine potently relax es human subcutaneous arterioles, and that most probably both muscular histamine H-2 receptors and endothelial histamine H, receptors, thus activating nitric oxide release, contribute to the relaxation. (C) 199 8 Elsevier Science B.V. All rights reserved.