Endothelium-independent relaxation induced by histamine in human dorsal penile artery

1. In vitro preparations of human dorsal penile arteries were used to evalu ate the effect of histamine and to characterize the histamine receptors inv olved in the response. 2. Cumulative administration of histamine induced a concentration-dependent relaxation in precontracted arteries. The H-1 receptor agonist 2-pyridylet hylamine induced a biphasic response: contraction followed by dilation. The H-2 receptor agonist dimaprit produced a marked relaxation. Mepyramine, a histamine H-1 receptor antagonist, led to a slight but statistically signif icant change in the pD(2) value corresponding to the relaxant phase of the H-1 receptor agonist and the histamine curve. The H-2 receptor antagonist c imetidine induced a marked shift in the dimaprit concentration-response cur ve without affecting the maximum response. Incubation with cimetidine led t o a considerable loss in the sensitivity of the arteries to histamine and i n the maximum relaxation. Combined treatment with histamine H-1 and H-2 rec eptor antagonists resulted in an additional displacement compared with the effect of each antagonist alone on the histamine response. The effects obse rved using a histamine H-3 receptor agonist and antagonist suggest that the involvement of this receptor is unlikely. 3. Removal of the endothelium was unable to reverse the histamine response. Pretreatment with N-G-nitro-L-arginine methyl ester, L-arginine and indome thacin had no effect on the histamine control curve. 4. In conclusion, the vasodilation of human dorsal penile artery induced by histamine seems to be mainly mediated by muscular histamine H-2 receptors, without the intervention of key intracellular mediators, such nitric oxide or relaxant prostanoids. A minor population of relaxant histamine H-1 rece ptors cannot be excluded.