Mechanisms involved in the vasorelaxing influence of histamine on isolated human subcutaneous resistance arteries.

The effects of histamine were analysed on human subcutaneous small arteries. No effect was seen on non-precontracted preparations. After precontraction (norepinephrine 1 microM and K+ 30 mM) histamine potently relaxed the arteries (EC50 = 0.3 microM; max. effect = 95% relaxation). The histamine H1 receptor antagonist, pyrilamine (10 microM), had only a small, non-significant inhibitory influence on histamine-induced relaxation while the histamine H2 receptor antagonist, cimetidine (0.1 mM), had a significant inhibitory influence. Relaxation was completely blocked in the presence of both antagonists. Both 2-pyridylethylamine (histamine H1 receptor agonist) and dimaprit (histamine H2 receptor agonist) elicited relaxation. Removal of endothelium reduced the relaxation effects of histamine and 2-pyridylethylamine, but not of dimaprit. Inhibition of nitric oxide synthesis by nitro-L-arginine significantly inhibited histamine-induced relaxation and even more clearly the cimetidine-resistant component. We conclude that histamine potently relaxes human subcutaneous arterioles, and that most probably both muscular histamine H2 receptors and endothelial histamine H1 receptors, thus activating nitric oxide release, contribute to the relaxation.