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CARDIOVASCULAR

Atypical -Adrenoceptor Subtypes Mediate Relaxations of Rabbit Corpus Cavernosum

Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil; and Department of Physical Education, Biosciences Institute, Universidade Estadual Paulista, Rio Claro, São Paulo, Brazil

This study was performed to characterize the -adrenoceptor population in rabbit isolated corpus cavernosum (RbCC) by using nonselective and selective -adrenoceptor agonists and antagonists in functional assays. Metaproterenol, ritodrine, fenoterol, and 8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(-methoxyphenyl)-1-methylethyl]amino]ethyl]carbostyril (TA 2005) (3–100 nmol each) dose dependently relaxed the RbCC preparations. These relaxations were markedly reduced by N-nitro-L-arginine methyl ester (L-NAME; 10 µM) and 1H-[1,2,4]-oxadiazolo-[4,3,-a]quinoxalin-1-one (ODQ) (10 µM), whereas the adenylyl cyclase inhibitor SQ 22,536 [9-(2-tetrahydrofuryl) adenine] (10 µM) had no effect. In contrast, neither L-NAME nor ODQ affected the isoproterenol-induced RbCC relaxations, but SQ 22,536 abolished this response. Sildenafil (1 µM) significantly potentiated the relaxations induced by ₂-agonists without affecting the isoproterenol-evoked relaxations. Rolipram (10 µM) enhanced the relaxations elicited by isoproterenol but had no effect on those induced by the selective ₂ agonists. Propranolol and (±)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride (ICI 118,551) determined a rightward shift in the concentration-response curves to isoproterenol in a noncompetitive manner with a reduction of maximum response at the highest antagonist concentration, with the slope values significantly different from unity. Propranolol and ICI 118,551 had no effect on the relaxations elicited by fenoterol, TA 2005, metaproterenol, and ritodrine. Atenolol and 1-[2-((3-carbamoyl-4-hydroxy)phenoxy) ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]-2-propanol methanesulfonate (CGP 20712A) (0.1–10 µM) failed to affect the relaxations induced by all tested -adrenoceptor agonists. Our study revealed the existence of two atypical -adrenoceptors in the rabbit erectile tissue. Isoproterenol relaxes the rabbit cavernosal tissue by activating atypical -adrenoceptors coupled to adenylyl cyclase pathway, whereas the selective ₂-adrenoceptor agonists relax the RbCC tissue through another atypical -adrenoceptor subtype coupled to nitric oxide release from the sinusoidal endothelium.

Address correspondence to: Dr. Edson Antunes, Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, P.O. Box 6111, 13084-971, Campinas (São Paulo), Brazil. E-mail: edson.antunes{at}uol.com.br

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