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Abstract

Volume 13, Issue 5 (September 2011) 13, 747–753; 10.1038/aja.2011.41

Relaxant effect and possible mechanism of 17-nor-subincanadine E in rabbit corpora cavernosa

Otacilio D Benvindo1, Nilberto RF Nascimento2, Claudia F Santos2, Manasses C Fonteles2, Edilberto R Silveira3, Daniel E Uchoa3, Adriana R Campos1, Karina MA Cunha1, Flavia A Santos1 and Vietla S Rao1

1 Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, PO Box 3157, 60430-270 Fortaleza, CE, Brazil
2 Superior Institute of Biomedicine, Ceara State University, Fortaleza, CE, Brazil
3 Department of Organic and Inorganic Chemistry, Federal University of Ceara, 60455-760 Fortaleza, CE, Brazil

Correspondence: Dr VSN Rao, (vietrao@ufc.br)

Received 15 December 2010; Revised 15 February 2011; Accepted 1 April 2011; Published online 18 July 2011

Abstract

Compounds with dual action on cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) may be a treatment option for erectile dysfunction, as they not only promote penile erection but also prevent the upregulation of phosphodiesterase-5. In this study, we examined the possible relaxant effect and mechanism of 17-nor-subincanadine E (SEC, 0.2-200 μmol l?1), a plant-derived alkaloid, in rabbit corpus cavernosum (RbCC) strips that had been precontracted by exposure to phenylephrine (10 μmol l?1) or a high concentration of K(+) (60 mmol l?1) in vitro. In addition to SEC's effect on cAMP and cGMP levels, electrical field stimulation (EFS) in phenylephrine-precontracted RbCC and calcium chloride (1-100 mmol l?1) evoked responses in depolarized RbCC were analysed. SEC relaxed the phenylephrine-precontracted RbCCs in a concentration-dependent manner. Atropine, guanethidine and N-ω-nitro-l-arginine methyl ester (L-NAME) did not have any effect on the relaxation of RBCCs. When 1H-(1, 2, 4)oxadiazole[4,3-a] quinoxalin-1-one (ODQ) was added, it effectively blocked the relaxant response of SEC. Although SEC enhanced the maximal relaxation produced by sodium nitroprusside (SNP) and forskolin in phenylephrine-precontracted cavernosal smooth muscle, it caused a decrease in the maximal contractile response induced by calcium chloride in depolarized RbCCs. The relaxant effect of SEC was paralleled by an increase in the tissue levels of the cyclic nucleotides cAMP and cGMP. We conclude that SEC promotes the relaxation of RbCC, possibly favouring cAMP and cGMP accumulation and calcium blockade. This novel mechanism could be useful for patients who do not benefit from phosphodiesterase inhibitors and for those with endothelial and nitrergic dysfunction, such as patients with diabetes, hypertension and dyslipidaemias.

Keywords: 17-nor-subincanadine E; cyclic nucleotides; electrical field stimulation; nitric oxide; rabbit corpus cavernosum; smooth muscle relaxation

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