Biphasic response to histamine in rabbit penile dorsal artery

The effects of specific histamine agonists and antagonists on isolated rabbit penile dorsal artery segments were explored using in vitro isometric techniques. Histamine caused the constriction of both precontracted and resting segments. In precontracted arterial rings treated with the H1 receptor antagonist mepyramine, histamine evoked a vasodilatation, followed by contraction at higher concentrations. The vasoconstrictor effect of histamine and the H1 receptor agonist, 2-pyridylethylamine (PEA) on preparations under conditions of basal tone, was competitively antagonized by mepyramine (10(-9)-10(-8) M). The relaxant effect of histamine, unmasked by mepyramine, was abolished by cimetidine. Dimaprit, the H2 receptor agonist, provoked a relaxation of precontracted segments that was also competitively inhibited by cimetidine (10(-6)-10(-5) M). Selective H3 receptor activation with the agonist (R)alpha-methylhistamine (10(-10)-10(-4) M) produced no effect in penile dorsal artery. The biphasic response to histamine was unaffected by endothelium removal or the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (3 x 10(-4) M) and its precursor, L-arginine (3 x 10(-4) M). Similarly, the cyclooxygenase inhibitor, indomethacin (3 x 10(-6) M) and a combination of Ca2+-activated K+ channel blockers apamin (5 x 10(-7) M) and charybdotoxin (10(-7) M) showed no effect on the histamine-induced relaxation or contraction. In conclusion, contraction, the predominant effect of histamine, is mediated by the activation of H1 receptors that mask the relaxant effect brought about by H2 receptors. Both these effects appear to be mediated by direct action on the smooth muscle, with no participation of nitric oxide or cyclooxygenase products or Ca2+-activated K+ channels.