Effects of phosphodiesterase inhibitors on the contractile responses of isolated human seminal vesicle tissue to adrenergic stimulation.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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 microM) were investigated on phasic contractions of SV tissue strips either mediated by means of electrical field stimulation (EFS) or the alpha(1)-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 >or= 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 microM rolipram, 5 microM sildenafil or vardenafil, and 8 microM vinpocetine.


CONCLUSIONS
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.
Uckert
Stefan
S
Division of Surgery, Department of Urology, Hannover Medical School, Hannover, Germany. sue_de_99@yahoo.de
Bazrafshan
Siamak
S
Sonnenberg
Joachim E
JE
Kuczyk
Markus A
MA
D018663:Adrenergic Agents / Q000494:pharmacology*; D000368:Aged; D000927:Anticonvulsants / Q000494:pharmacology; D004542:Ejaculation / Q000187:drug effects; D004558:Electric Stimulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D012669:Seminal Vesicles / Q000187:drug effects*; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology
D018663:Adrenergic Agents; D000927:Anticonvulsants; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014748:Vinca Alkaloids; C013983:vinpocetine; D000068677:Sildenafil Citrate