Comparative Relaxing Effects of Sildenafil, Vardenafil, and Tadalafil in Human Corpus Cavernosum

Contribution of Endogenous Nitric Oxide Release

Haroldo Alfredo Flores Toque, Fernanda Priviero, Cleber E. Teixeira, Mário A. Claudino, Juliana S. Baracat, Adriano Fregonesi, Gilberto De Nucci, Edson Antunes

Research output: Contribution to journalArticle

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Abstract

Objectives: To compare the direct relaxant activity of sildenafil, vardenafil, and tadalafil in the human corpus cavernosum (HCC) and to investigate their modulatory effects on nitric oxide (NO)-mediated responses. Phosphodiesterase (PDE)-5 inhibitors cause cavernosal smooth muscle relaxation and penile erection. Methods: HCC strips were mounted in 10-mL organ baths containing Krebs solution and connected to force-displacement transducers. The changes in isometric force were recorded using the Powerlab 400 data acquisition system. Corporeal smooth muscle was precontracted submaximally with phenylephrine (10 μmol/L). Results: All PDE-5 inhibitors tested (0.001-10 μmol/L) relaxed phenylephrine-precontracted HCC with similar values of potency in a concentration-dependent manner. However, the maximal relaxations induced by tadalafil (83% ± 4%) were significantly lower compared with sildenafil (107% ± 5%) and vardenafil (111% ± 3%). The NO synthesis inhibitor N-nitro-l-arginine methyl ester (100 μmol/L) caused significant rightward shifts in the concentration-response curves for sildenafil (4.0-fold), vardenafil (4.6-fold), and tadalafil (3.2-fold) in HCC tissue. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 μmol/L) also produced similar rightward shifts for these PDE-5 inhibitors. The cavernosal relaxations evoked by either acetylcholine or the NO donor glyceryl trinitrate were markedly potentiated by sildenafil, vardenafil, and tadalafil (0.1 μmol/L each). All PDE-5 inhibitors significantly increased the duration of electrical field stimulation-induced relaxations (8 Hz). Conclusions: Our findings have shown that sildenafil, vardenafil, and tadalafil relax HCC tissues in a concentration-dependent manner, but the maximal relaxation obtained with tadalafil was significantly lower than that obtained with sildenafil and vardenafil. Moreover, the PDE-5 inhibitors interacted with endogenous and exogenous NO, amplifying its HCC relaxation.

Original languageEnglish (US)
Pages (from-to)216-221
Number of pages6
JournalUrology
Volume74
Issue number1
DOIs
StatePublished - Jul 1 2009

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Phosphodiesterase 5 Inhibitors
Nitric Oxide
Phenylephrine
Smooth Muscle
Penile Erection
Muscle Relaxation
Nitric Oxide Donors
Guanylate Cyclase
Nitroglycerin
Transducers
Baths
Information Systems
Electric Stimulation
Acetylcholine
Sildenafil Citrate
Tadalafil
Vardenafil Dihydrochloride

ASJC Scopus subject areas

  • Urology

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Comparative Relaxing Effects of Sildenafil, Vardenafil, and Tadalafil in Human Corpus Cavernosum : Contribution of Endogenous Nitric Oxide Release. / Flores Toque, Haroldo Alfredo; Priviero, Fernanda; Teixeira, Cleber E.; Claudino, Mário A.; Baracat, Juliana S.; Fregonesi, Adriano; De Nucci, Gilberto; Antunes, Edson.

In: Urology, Vol. 74, No. 1, 01.07.2009, p. 216-221.

Research output: Contribution to journalArticle

Flores Toque, Haroldo Alfredo ; Priviero, Fernanda ; Teixeira, Cleber E. ; Claudino, Mário A. ; Baracat, Juliana S. ; Fregonesi, Adriano ; De Nucci, Gilberto ; Antunes, Edson. / Comparative Relaxing Effects of Sildenafil, Vardenafil, and Tadalafil in Human Corpus Cavernosum : Contribution of Endogenous Nitric Oxide Release. In: Urology. 2009 ; Vol. 74, No. 1. pp. 216-221.
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abstract = "Objectives: To compare the direct relaxant activity of sildenafil, vardenafil, and tadalafil in the human corpus cavernosum (HCC) and to investigate their modulatory effects on nitric oxide (NO)-mediated responses. Phosphodiesterase (PDE)-5 inhibitors cause cavernosal smooth muscle relaxation and penile erection. Methods: HCC strips were mounted in 10-mL organ baths containing Krebs solution and connected to force-displacement transducers. The changes in isometric force were recorded using the Powerlab 400 data acquisition system. Corporeal smooth muscle was precontracted submaximally with phenylephrine (10 μmol/L). Results: All PDE-5 inhibitors tested (0.001-10 μmol/L) relaxed phenylephrine-precontracted HCC with similar values of potency in a concentration-dependent manner. However, the maximal relaxations induced by tadalafil (83{\%} ± 4{\%}) were significantly lower compared with sildenafil (107{\%} ± 5{\%}) and vardenafil (111{\%} ± 3{\%}). The NO synthesis inhibitor N-nitro-l-arginine methyl ester (100 μmol/L) caused significant rightward shifts in the concentration-response curves for sildenafil (4.0-fold), vardenafil (4.6-fold), and tadalafil (3.2-fold) in HCC tissue. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 μmol/L) also produced similar rightward shifts for these PDE-5 inhibitors. The cavernosal relaxations evoked by either acetylcholine or the NO donor glyceryl trinitrate were markedly potentiated by sildenafil, vardenafil, and tadalafil (0.1 μmol/L each). All PDE-5 inhibitors significantly increased the duration of electrical field stimulation-induced relaxations (8 Hz). Conclusions: Our findings have shown that sildenafil, vardenafil, and tadalafil relax HCC tissues in a concentration-dependent manner, but the maximal relaxation obtained with tadalafil was significantly lower than that obtained with sildenafil and vardenafil. Moreover, the PDE-5 inhibitors interacted with endogenous and exogenous NO, amplifying its HCC relaxation.",
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T2 - Contribution of Endogenous Nitric Oxide Release

AU - Flores Toque, Haroldo Alfredo

AU - Priviero, Fernanda

AU - Teixeira, Cleber E.

AU - Claudino, Mário A.

AU - Baracat, Juliana S.

AU - Fregonesi, Adriano

AU - De Nucci, Gilberto

AU - Antunes, Edson

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N2 - Objectives: To compare the direct relaxant activity of sildenafil, vardenafil, and tadalafil in the human corpus cavernosum (HCC) and to investigate their modulatory effects on nitric oxide (NO)-mediated responses. Phosphodiesterase (PDE)-5 inhibitors cause cavernosal smooth muscle relaxation and penile erection. Methods: HCC strips were mounted in 10-mL organ baths containing Krebs solution and connected to force-displacement transducers. The changes in isometric force were recorded using the Powerlab 400 data acquisition system. Corporeal smooth muscle was precontracted submaximally with phenylephrine (10 μmol/L). Results: All PDE-5 inhibitors tested (0.001-10 μmol/L) relaxed phenylephrine-precontracted HCC with similar values of potency in a concentration-dependent manner. However, the maximal relaxations induced by tadalafil (83% ± 4%) were significantly lower compared with sildenafil (107% ± 5%) and vardenafil (111% ± 3%). The NO synthesis inhibitor N-nitro-l-arginine methyl ester (100 μmol/L) caused significant rightward shifts in the concentration-response curves for sildenafil (4.0-fold), vardenafil (4.6-fold), and tadalafil (3.2-fold) in HCC tissue. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 μmol/L) also produced similar rightward shifts for these PDE-5 inhibitors. The cavernosal relaxations evoked by either acetylcholine or the NO donor glyceryl trinitrate were markedly potentiated by sildenafil, vardenafil, and tadalafil (0.1 μmol/L each). All PDE-5 inhibitors significantly increased the duration of electrical field stimulation-induced relaxations (8 Hz). Conclusions: Our findings have shown that sildenafil, vardenafil, and tadalafil relax HCC tissues in a concentration-dependent manner, but the maximal relaxation obtained with tadalafil was significantly lower than that obtained with sildenafil and vardenafil. Moreover, the PDE-5 inhibitors interacted with endogenous and exogenous NO, amplifying its HCC relaxation.

AB - Objectives: To compare the direct relaxant activity of sildenafil, vardenafil, and tadalafil in the human corpus cavernosum (HCC) and to investigate their modulatory effects on nitric oxide (NO)-mediated responses. Phosphodiesterase (PDE)-5 inhibitors cause cavernosal smooth muscle relaxation and penile erection. Methods: HCC strips were mounted in 10-mL organ baths containing Krebs solution and connected to force-displacement transducers. The changes in isometric force were recorded using the Powerlab 400 data acquisition system. Corporeal smooth muscle was precontracted submaximally with phenylephrine (10 μmol/L). Results: All PDE-5 inhibitors tested (0.001-10 μmol/L) relaxed phenylephrine-precontracted HCC with similar values of potency in a concentration-dependent manner. However, the maximal relaxations induced by tadalafil (83% ± 4%) were significantly lower compared with sildenafil (107% ± 5%) and vardenafil (111% ± 3%). The NO synthesis inhibitor N-nitro-l-arginine methyl ester (100 μmol/L) caused significant rightward shifts in the concentration-response curves for sildenafil (4.0-fold), vardenafil (4.6-fold), and tadalafil (3.2-fold) in HCC tissue. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 μmol/L) also produced similar rightward shifts for these PDE-5 inhibitors. The cavernosal relaxations evoked by either acetylcholine or the NO donor glyceryl trinitrate were markedly potentiated by sildenafil, vardenafil, and tadalafil (0.1 μmol/L each). All PDE-5 inhibitors significantly increased the duration of electrical field stimulation-induced relaxations (8 Hz). Conclusions: Our findings have shown that sildenafil, vardenafil, and tadalafil relax HCC tissues in a concentration-dependent manner, but the maximal relaxation obtained with tadalafil was significantly lower than that obtained with sildenafil and vardenafil. Moreover, the PDE-5 inhibitors interacted with endogenous and exogenous NO, amplifying its HCC relaxation.

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