Effects of Phosphodiesterase Inhibitors on Contraction Induced by Endothelin-1 of Isolated Human Prostatic Tissue

Abstract

To study the effects of selective phosphodiesterase (PDE) inhibitors on the contraction induced by endothelin-1 (ET-1) of isolated human prostatic tissue. Using the organ bath technique, the effects of the cumulative addition of the PDE1 inhibitor vinpocetine, PDE2 inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA), PDE4 inhibitor rolipram, and PDE5 inhibitors sildenafil, vardenafil, and tadalafil (1 nM to 10 microM) were investigated on the contraction brought about by the peptide ET-1 (1 microM) on normal human prostatic tissue isolated from the transition zone. In the present study, the nitric oxide donor drug sodium nitroprusside and adenylyl cyclase activator forskolin were used as reference compounds. ET-1 induced stable and long-lasting contraction of the isolated prostatic tissue. The tension induced by ET-1 was dose-dependently reversed by the drugs with the following rank order of efficacy: rolipram, forskolin, tadalafil, sodium nitroprusside, sildenafil, vinpocetine, vardenafil, EHNA. The maximal reversion of tension ranged from 67% (rolipram) to 20% (EHNA). Our results have provide additional evidence that the function of prostatic smooth muscle is under the control of peptidergic and cyclic nucleotide (cyclic guanosine monophosphate, cyclic adenosine monophosphate)-mediated pathways. This might give a rationale for the use of drugs interacting with cyclic guanosine monophosphate or cyclic adenosine monophosphate signaling, such as PDE inhibitors or nitric oxide donors, in the pharmacotherapy of the benign prostatic syndrome.