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Effects of Phosphodiesterase Inhibitors on the Contractile Responses of Isolated Human Seminal Vesicle Tissue to Adrenergic Stimulation

Authors


Stefan Ückert, PhD, Department of Urology, Hannover Medical School, 30623 Hannover, Germany. Tel: +49 511 5 32 34 37; Fax: +49 511 5 32 84 37; E-mail: sue_de_99@yahoo.de

ABSTRACT

Introduction.  It has been suggested that the capability of the phosphodiesterase 5 (PDE5) inhibitor sildenafil citrate (VIAGRA) to retard the ejaculatory response may include modulation of the contraction of seminal vesicle (SV) smooth muscle. In fact, it has been shown that PDE inhibitors can reverse the tension of isolated human SV tissue and enhance the production of cyclic AMP and cyclic GMP.

Aim.  The aim of this study was to examine the effects of selective phosphodiesterase (PDE) inhibitors on both the spontaneous and electrically induced phasic contractions of isolated human SV smooth muscle.

Main Outcome Measures.  To measure the inhibition exerted by PDE inhibitors vinpocetine (PDE1-inhibitor), rolipram (PDE4-inhibitor), sildenafil, and vardenafil (PDE5-inhibitors) on the phasic contractile response of isolated SV tissue.

Methods.  Using the organ bath technique, the effects of increasing concentrations of the PDE inhibitors (1 nM–10 µM) were investigated on phasic contractions of SV tissue strips either mediated by means of electrical field stimulation (EFS) or the alpha1-adrenoceptor agonist norepinephrine.

Results.  The contractile activity in response to EFS was dose-dependently reversed by the PDE inhibitors. The rank order of efficacy was: rolipram > sildenafil ≥ vardenafil > vinpocetine. Mean maximum inhibition of contraction was determined as −89.6% (rolipram), −61.3% (sildenafil), −62% (vardenafil), and −46% (vinpocetine). No differences were registered with regard to the effects of sildenafil and vardenafil on the inhibition of the contraction amplitudes. The frequency of the spontaneous contractions (amplitudes/5 minutes) was reduced by 50% in the presence of 2 µM rolipram, 5 µM sildenafil or vardenafil, and 8 µM vinpocetine.

Conclusion.  Our results demonstrate that PDE inhibitors can inhibit EFS-induced and spontaneous contractile activity of isolated human SV tissue. These findings might be of importance with regard to the pharmacological treatment of premature ejaculation.Ückert S, Bazrafshan S, Sonnenberg JE, and Kuczyk MA. Effects of phosphodiesterase inhibitors on the contractile responses of isolated human seminal vesicle tissue to adrenergic stimulation. J Sex Med 2009;6:408–414.

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