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 erectio n 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 i ncrease in intracavernosal pressure (ICP) and the increase in ICP induced b y pinacidil with acetylcholine, PGE1 or L-arginine was more pronounced than with the compounds alone. Furthermore, pinacidil (1 mmol/L) effectively re versed 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 c ases 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 f eline erectile tissue in vivo, probably via increased K+ permeability and s ubsequent hyperpolarization. Further comparative studies with erectogenic c ompounds on human erectile tissue and clinical testing are required to dete rmine whether K+-channel openers can be used in the diagnosis and treatment of erectile dysfunction. However, pinacidil seems promising as an intracav ernosal agent combined with PGE1 to produce synergistic effects.