作者
José Luis Ruiz Rubio,Medardo Hernández,Luis Rivera,Ana Cristina Martı́nez,Albino García‐Sacristán,Dolores Prieto
摘要
No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Feb 2004Mechanisms of Prostaglandin E1-Induced Relaxation in Penile Resistance Arteries JOSÉ L. RUIZ RUBIO, MEDARDO HERNÁNDEZ, LUIS RIVERA DE LOS ARCOS, A. CRISTINA MARTÍNEZ, ALBINO GARCÍA-SACRISTÁN, and DOLORES PRIETO JOSÉ L. RUIZ RUBIOJOSÉ L. RUIZ RUBIO , MEDARDO HERNÁNDEZMEDARDO HERNÁNDEZ , LUIS RIVERA DE LOS ARCOSLUIS RIVERA DE LOS ARCOS , A. CRISTINA MARTÍNEZA. CRISTINA MARTÍNEZ , ALBINO GARCÍA-SACRISTÁNALBINO GARCÍA-SACRISTÁN , and DOLORES PRIETODOLORES PRIETO View All Author Informationhttps://doi.org/10.1097/01.ju.0000097496.27675.c4AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The current in vitro study was performed to investigate intracellular mechanisms underlying prostaglandin E1 (PGE1) elicited vasodilation in isolated penile resistance arteries and evaluate whether there may be interactions with the nitric oxide (NO)/cyclic guanosine 3′,5′-monophosphate (cGMP) pathway. Materials and Methods: Second or third order branches of the horse deep intracavernous penile artery were mounted in microvascular myographs. The vasodilator effects of PGE1 and cyclic adenosine 3′,5′-monophosphate (cAMP) elevating agents were evaluated in the absence and the presence of inhibitors of the adenylate cyclase/cAMP and the NO/cGMP pathways. Results: PGE1, the adenylate cyclase activator forskolin, and the phosphodiesterase types 3 and 4 inhibitors milrinone and rolipram, respectively, dose dependently relaxed penile resistance arteries with rolipram being the most potent of the 4 relaxant agents. Threshold concentrations of rolipram markedly enhanced PGE1 elicited relaxations. The inhibition of cAMP dependent protein kinase decreased relaxant responses to PGE1, forskolin and rolipram. Neither mechanical endothelial cell removal nor the blockade of NO synthase or guanylate cyclase altered PGE1 relaxant responses. However, combined treatment with blockers of cAMP dependent protein kinase and cGMP dependent protein kinase unmasked an inhibitory effect of the latter on relaxations induced by PGE1 and forskolin. Conclusions: These results provide evidence for cAMP involvement in PGE1 elicited vasodilation of penile resistance arteries. They underline the importance of the adenylate cyclase/cAMP pathway in the relaxation of penile erectile tissue. Moreover, cAMP elevating agents seem to cross-activate cGMP dependent protein kinase, thus, interacting downstream with the NO/cGMP cascade. References 1 : The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience. J Urol1996; 155: 802. Link, Google Scholar 2 : Pharmacology of penile erection. Pharmacol Rev2001; 53: 417. Google Scholar 3 : Rationale for the combination of PGE(1) and S-nitroso-glutathione to induce relaxation of human penile smooth muscle. J Pharmacol Exp Ther2000; 295: 586. Google Scholar 4 : Characterization of cyclic AMP accumulation in cultured human corpus cavernosum smooth muscle cells. J Urol1994; 152: 1308. Abstract, Google Scholar 5 : Misoprostol induces relaxation of human corpus cavernosum smooth muscle: comparison to prostaglandin E1. Int J Impot Res2000; 12: 107. Google Scholar 6 : Penile arteries and erection. J Vasc Res2002; 39: 283. Google Scholar 7 : The biochemical and neurologic basis for the treatment of erectile dysfunction. J Pharmacol Exp Ther2001; 296: 225. Google Scholar 8 : Cross-regulation of intracellular cGMP and cAMP in cultured human corpum cavernosum smooth muscle cells. Mol Cell Biol Res Com2000; 4: 10. Google Scholar 9 : Contribution of K+ channels and ouabain-sensitive mechanisms to the endothelium-dependent relaxations of horse penile small arteries. Br J Pharmacol1998; 123: 1609. Google Scholar 10 : cAMP-dependent protein kinase is in an active state in rat small arteries possessing a myogenic tone. Am J Physiol1999; 277: H1145. Google Scholar 11 : Regulation of human penile smooth muscle tone by prostanoid receptors. Br J Pharmacol2002; 136: 23. Google Scholar 12 : The effect of the specific phosphodiesterase (PDE) inhibitors on human and rabbit cavernous tissue in vitro and in vivo. J Urol1998; 159: 1390. Link, Google Scholar 13 : Smooth muscle tone regulation in rabbit cavernosal and spongiosal tissue by cyclic AMP- and cyclic GMP-dependent mechanisms. J Urol1994; 152: 2159. Abstract, Google Scholar 14 : Effect of sildenafil on non-adrenergic non-cholinergic neurotransmission in bovine penile small arteries. Eur J Pharmacol2001; 412: 155. Google Scholar 15 : Potentiation of erectile response and cAMP accumulation by combination of prostaglandin E1 and rolipram, a selective inhibitor of the type 4 phosphodiesterase (PDE 4). J Urol1999; 162: 1848. Link, Google Scholar 16 : Nitric oxide is involved in the inhibitory neurotransmission and endothelium-dependent relaxations of human small penile arteries. Clin Sci1997; 92: 269. Google Scholar 17 : Cyclic AMP and mechanisms of vasodilation. Pharmacol Ther1990; 47: 329. Google Scholar 18 : Repeated PGE1 treatment enhances nitric oxide and erection responses to nerve stimulation in the rat penis by upregulating constitutive NOS isoforms. J Urol1999; 162: 2205. Abstract, Google Scholar 19 : Direct evidence for cross-activation of cGMP-dependent protein kinase by cAMP in pig coronary arteries. J Biol Chem1992; 267: 1015. Google Scholar 20 : Prostacyclin-induced vasodilation in rabbit heart is mediated by ATP-sensitive potassium channels. Am J Physiol1993; 264: H238. Google Scholar 21 : Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. Proc Natl Acad Sci USA2000; 97: 2349. Google Scholar From the Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense and Departamento de Urología, Hospital Universitario Ramón y Cajal, Madrid, Spain© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 171Issue 2February 2004Page: 968-973 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordsvascular resistancehorsesarteriesalprostadilpenisMetricsAuthor Information JOSÉ L. RUIZ RUBIO More articles by this author MEDARDO HERNÁNDEZ More articles by this author LUIS RIVERA DE LOS ARCOS More articles by this author A. CRISTINA MARTÍNEZ More articles by this author ALBINO GARCÍA-SACRISTÁN More articles by this author DOLORES PRIETO More articles by this author Expand All Advertisement PDF downloadLoading ...