Biphasic response to histamine in rabbit penile dorsal artery

The effects of specific histamine agonists and antagonists on isolated rabb it penile dorsal artery segments were explored using in vitro isometric tec hniques. Histamine caused the constriction of both precontracted and restin g segments. In precontracted arterial rings treated with the H-1 receptor a ntagonist mepyramine, histamine evoked a vasodilatation, followed by contra ction at higher concentrations. The vasoconstrictor effect of histamine and the H-1 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 H-2 receptor agonist, provoked a re laxation of precontracted segments that was also competitively inhibited by cimetidine (10(-6)-10(-5) M). Selective H-3 receptor activation with the a gonist (R)alpha -methylhistamine (10(-10)-10(-4) M) produced no effect in p enile dorsal artery. The biphasic response to histamine was unaffected by e ndothelium removal or the nitric oxide inhibitor N-G-nitro-L-arginine methy l 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 rela xation or contraction. In conclusion, contraction, the predominant effect o f histamine, is mediated by the activation of H-1 receptors that mask the r elaxant effect brought about by H-2 receptors. Both these effects appear to be mediated by direct action on the smooth muscle, with no participation o f nitric oxide or cyclooxygenase products or Ca2+-activated K+ channels.