Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/198336
Type: Artigo de periódico
Title: Effect Of The Phosphodiesterase 5 Inhibitors Sildenafil, Tadalafil And Vardenafil On Rat Anococcygeus Muscle: Functional And Biochemical Aspects.
Author: Toque, Haroldo A
Priviero, Fernanda B M
Zemse, Saiprasad M
Antunes, Edson
Teixeira, Cleber E
Webb, R Clinton
Abstract: 1. 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 micromol/L) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 micromol/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 micromol/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 micromol/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 micromol/L. There were no significant differences between the effects of the three PDE5 inhibitors. 6. Vardenafil (0.01-0.1 micromol/L) was more potent in preventing cGMP degradation in vitro than sildenafil (0.01-0.1 micromol/L) and tadalafil (0.01-0.1 micromol/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.
Subject: Animals
Carbolines
Drug Evaluation, Preclinical
Enzyme Inhibitors
Guanylate Cyclase
Imidazoles
Male
Muscle Contraction
Muscle, Smooth
Ng-nitroarginine Methyl Ester
Nitroglycerin
Oxadiazoles
Penile Erection
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Piperazines
Purines
Quinoxalines
Rats
Rats, Sprague-dawley
Sulfones
Triazines
Vasodilator Agents
Rights: fechado
Identifier DOI: 10.1111/j.1440-1681.2008.05071.x
Address: http://www.ncbi.nlm.nih.gov/pubmed/18986324
Date Issue: 2009
Appears in Collections:Unicamp - Artigos e Outros Documentos

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