A KATP-channel opener as a potential treatment modality for erectile dysfunction

Authors


Dr Kim Department of Urology, Korea University Hospital, 126–1, 5-ka, Anam-dong, Sungbuk-ku, Seoul 136–705, Korea.

Abstract

Objectives

To assess the effects of pinacidil (a KATP-channel opener) for the treatment of penile erectile dysfunction and to examine the role of the K+-channel in cavernosal smooth muscle contractility.

Materials and methods

Using a feline model, the magnitude of penile erection caused by pinacidil was compared with that caused by erectogenic drugs, e.g. acetylcholine, prostaglandin E1 (PGE1) and l-arginine. The effects of K+-channel blockers (4-aminopyridine, glibenclamide and tetraethylammonium) and pinacidil on penile erections induced by the drugs were investigated.

Results

The intra-arterial injection of pinacidil caused a dose-dependent increase in intracavernosal pressure (ICP) and the increase in ICP induced by pinacidil with acetylcholine, PGE1 or l-arginine was more pronounced than with the compounds alone. Furthermore, pinacidil (1 mmol/L) effectively reversed the inhibitory effects of the K+-channel blockers on the cavernosal relaxation induced by acetylcholine, PGE1 or l-arginine (P<0.01). Notably, pinacidil induced cavernosal relaxation after injecting the drugs even in cases refractory to higher concentrations (0.1 mol/L) of the drugs (n=11, P<0.01).

Conclusions

These results suggest that pinacidil is effective in relaxing feline erectile tissue in vivo, probably via increased K+ permeability and subsequent hyperpolarization. Further comparative studies with erectogenic compounds on human erectile tissue and clinical testing are required to determine whether K+-channel openers can be used in the diagnosis and treatment of erectile dysfunction. However, pinacidil seems promising as an intracavernosal agent combined with PGE1 to produce synergistic effects.

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