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Endothelium‐Independent Relaxation Induced By Histamine In Human Dorsal Penile Artery
Author(s) -
Martínez Ac,
Prieto D,
Raposo R,
Delgado Ja,
Resel L,
GarcíaSacristán A,
Benedito S
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03280.x
Subject(s) - dimaprit , histamine , cimetidine , histamine h1 receptor , agonist , histamine receptor , medicine , endocrinology , chemistry , mepyramine , histamine h2 receptor , pharmacology , receptor , antagonist
SUMMARY 1. In vitro preparations of human dorsal penile arteries were used to evaluate the effect of histamine and to characterize the histamine receptors involved in the response. 2. Cumulative administration of histamine induced a concentration‐dependent relaxation in precontracted arteries. The H 1 receptor agonist 2‐pyridylethylamine 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 significant 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 cimetidine induced a marked shift in the dimaprit concentration–response curve without affecting the maximum response. Incubation with cimetidine led to a considerable loss in the sensitivity of the arteries to histamine and in the maximum relaxation. Combined treatment with histamine H 1 and H 2 receptor antagonists resulted in an additional displacement compared with the effect of each antagonist alone on the histamine response. The effects observed 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 indomethacin 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 receptors cannot be excluded.