EFFECT OF THE PHOSPHODIESTERASE 5 INHIBITORS SILDENAFIL, TADALAFIL AND VARDENAFIL ON RAT ANOCOCCYGEUS MUSCLE: FUNCTIONAL AND BIOCHEMICAL ASPECTS

dc.creatorToque, HA
dc.creatorPriviero, FBM
dc.creatorZemse, SM
dc.creatorAntunes, E
dc.creatorTeixeira, CE
dc.creatorWebb, C
dc.date2009
dc.dateAPR
dc.date2014-11-18T19:57:40Z
dc.date2015-11-26T17:53:42Z
dc.date2014-11-18T19:57:40Z
dc.date2015-11-26T17:53:42Z
dc.date.accessioned2018-03-29T00:37:17Z
dc.date.available2018-03-29T00:37:17Z
dc.identifierClinical And Experimental Pharmacology And Physiology. Wiley-blackwell Publishing, Inc, v. 36, n. 4, n. 358, n. 366, 2009.
dc.identifier0305-1870
dc.identifierWOS:000265549100002
dc.identifier10.1111/j.1440-1681.2008.05071.x
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/63960
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/63960
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/63960
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1290594
dc.description1. The anococcygeus muscle is part of the erectile machinery in male rodents. Phosphodiesterase (PDE) 5 inhibitors enhance and prolong the effects of cGMP, which has a key role in penile erection. The aim of the present study was to provide a functional and biochemical comparison of the three PDE5 inhibitors, namely sildenafil, tadalafil and vardenafil, in the rat anococcygeus muscle. 2. Muscle strips were mounted in 4 mL organ baths and isometric force recorded. Levels of cGMP were measured using an enzyme immunoassay kit. Western blots were used to determine PDE5 protein expression. 3. The PDE5 inhibitors concentration-dependently relaxed carbachol-precontracted anococcygeus muscle; however, vardenafil was more potent (pEC(50) =8.11 +/- 0.05) than sildenafil (7.72 +/- 0.06) or tadalafil (7.69 +/- 0.05). Addition of N(G)-nitro-L-arginine methyl ester (100 mu mol/L) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 mu mol/L) to the organ baths caused significant rightward shifts in concentration-response curves for all PDE5 inhibitors. 4. Sildenafil, tadalafil and vardenafil (all at 0.1 mu mol/L) caused leftward shifts in the glyceryl trinitrate (GTN) concentration-response curves (by 4.0-, 3.7- and 5.5-fold, respectively). In addition, all three PDE5 inhibitors significantly potentiated relaxation responses to both GTN (0.01-10 mu mol/L) and electrical field stimulation (EFS; 1-32 Hz), with vardenafil having more pronounced effects. 5. All three PDE5 inhibitors reduced EFS-evoked contractions in a concentration-dependent manner over the concentration range 0.001-1 mu mol/L. There were no significant differences between the effects of the three PDE5 inhibitors. 6. Vardenafil (0.01-0.1 mu mol/L) was more potent in preventing cGMP degradation in vitro than sildenafil (0.01-0.1 mu mol/L) and tadalafil (0.01-0.1 mu mol/L). 7. Under control conditions, the expression of PDE5 was higher in the anococcygeus muscle than in the corpus cavernosum. 8. In conclusion, PDE5 inhibitors enhance exogenous and endogenous nitric oxide-mediated relaxation in the rat anococcygeus muscle. The potency of vardenafil was greater than that of either sildenafil or tadalafil.
dc.description36
dc.description4
dc.description358
dc.description366
dc.languageen
dc.publisherWiley-blackwell Publishing, Inc
dc.publisherMalden
dc.publisherEUA
dc.relationClinical And Experimental Pharmacology And Physiology
dc.relationClin. Exp. Pharmacol. Physiol.
dc.rightsfechado
dc.rightshttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.sourceWeb of Science
dc.subjectanococcygeus muscle
dc.subjectcGMP
dc.subjectnitric oxide
dc.subjectphosphodiestarase 5
dc.subjectNitric-oxide Synthases
dc.subjectErectile-dysfunction
dc.subjectType-5 Inhibitors
dc.subjectCorpus Cavernosum
dc.subjectIn-vitro
dc.subjectNitrergic Transmission
dc.subjectNerve-stimulation
dc.subjectRelaxation
dc.subjectSystem
dc.subjectRabbit
dc.titleEFFECT OF THE PHOSPHODIESTERASE 5 INHIBITORS SILDENAFIL, TADALAFIL AND VARDENAFIL ON RAT ANOCOCCYGEUS MUSCLE: FUNCTIONAL AND BIOCHEMICAL ASPECTS
dc.typeArtículos de revistas


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