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EFFECT OF THE PHOSPHODIESTERASE 5 INHIBITORS SILDENAFIL, TADALAFIL AND VARDENAFIL ON RAT ANOCOCCYGEUS MUSCLE: FUNCTIONAL AND BIOCHEMICAL ASPECTS
Author(s) -
Toque Haroldo A,
Priviero Fernanda BM,
Zemse Saiprasad M,
Antunes Edson,
Teixeira Cleber E,
Webb R Clinton
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.05071.x
Subject(s) - vardenafil , tadalafil , sildenafil , cgmp specific phosphodiesterase type 5 , chemistry , erectile dysfunction , pharmacology , medicine , endocrinology , phosphodiesterase , enzyme , biochemistry
SUMMARY1 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 µmol/L) or 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (10 µmol/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 µmol/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 µmol/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 µmol/L. There were no significant differences between the effects of the three PDE5 inhibitors. 6 Vardenafil (0.01–0.1 µmol/L) was more potent in preventing cGMP degradation in vitro than sildenafil (0.01–0.1 µmol/L) and tadalafil (0.01–0.1 µmol/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.