Endothelium‐Independent Relaxation Induced By Histamine In Human Dorsal Penile Artery

Clinical and Experimental Pharmacology and Physiology - Tập 27 Số 7 - Trang 500-507 - 2000
Ana Cristina Martı́nez1, Dolores Prieto1, Rafaela Raposo1, Jose Angel Delgado1, Luis Resel1, Albino García‐Sacristán1, Sara Benedito1
1Department of Physiology, *Pharmacy and †Veterinary Faculties and ‡Department of Urology, San Carlos Hospital, Complutense University, Madrid, Spain

Tóm tắt

SUMMARY1. 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 H1 receptor agonist 2‐pyridylethylamine induced a biphasic response: contraction followed by dilation. The H2 receptor agonist dimaprit produced a marked relaxation. Mepyramine, a histamine H1 receptor antagonist, led to a slight but statistically significant change in the pD2 value corresponding to the relaxant phase of the H1 receptor agonist and the histamine curve. The H2 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 H1 and H2 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 H3 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 NG‐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 H2 receptors, without the intervention of key intracellular mediators, such nitric oxide or relaxant prostanoids. A minor population of relaxant histamine H1 receptors cannot be excluded.

Từ khóa


Tài liệu tham khảo

10.1159/000159206

10.1016/S0022-5347(01)64780-3

10.1042/cs0920269

10.1111/j.1476-5381.1995.tb17211.x

10.1038/sj.bjp.0701780

10.3109/01485019108987633

Adaikan PG, 1991, Physio‐pharmacology of human penile erection: Autonomic/nitrergic neurotransmissions and receptors of the human corpus cavernosum., Asia Pacific J. Pharmacol., 6, 213

10.1016/0014-2999(77)90008-5

Kirkeby HJ, 1989, Effects of noradrenaline, 5‐hydroxytryptamine and histamine on human penile cavernous tissue and circumflex veins., Int. J. Impot. Res., 1, 181

10.1152/physrev.1995.75.1.191

Andersson KE, 1990, Mechanism for contraction and relaxation of human penile smooth muscle. Int. J. Impot., Res., 2, 209

10.1038/sj.bjp.0701883

Segarra G, 1998, Role of vasopressin on adrenergic neurotransmission in human penile blood vessels., J. Pharmacol. Exp. Ther., 286, 1315

10.1042/CS19980207

Kogan MI, 1995, Arterial factors in the mechanism of penile erection., Urol. Nefrol., 2, 37

10.1111/j.1748-1716.1983.tb07178.x

KenakinTP.Pharmacological Analysis of Drug–Receptor Interaction. Raven Press New York. 1987.

10.1111/j.1365-2125.1989.tb05344.x

10.1046/j.1468-2982.1991.1104183.x

10.2170/jjphysiol.45.607

Benedito S, 1991, Histamine induces endothelium‐dependent relaxation of bovine retinal arteries., Invest. Ophthalmol. Vis. Sci., 32, 32

10.1016/S0014-2999(97)85411-8

10.1111/j.1748-1716.1988.tb08302.x

Jacobsen K, 1994, Studies on responses to potassium, noradrenaline, serotonin, histamine and prostaglandin F2α, of isolated pudendal arteries from non‐lactating goats., Comp. Biochem. Physiol., 109, 67

10.1046/j.1365-2680.1998.18488.x

10.1016/S0014-2999(97)10105-4

10.1007/s000110050399

Hill SJ, 1997, Classification of histamine receptors., Pharmacol. Rev., 49, 253

10.1016/S0014-2999(98)00179-4

10.1089/jop.1995.11.167

10.1016/S0014-2999(97)81941-3

10.1016/0014-2999(88)90026-X

10.1111/j.1476-5381.1994.tb14756.x

10.1111/j.1464-410X.1995.tb07315.x

10.1097/00005344-199101000-00013

10.1016/0014-2999(86)90738-7