A K(ATP)-channel opener as a potential treatment modality for erectile dysfunction

Objectives. To assess the effects of pinacidil (a K(ATP)-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.