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


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.
Moon
D G
DG
Department of Urology, Korea University Hospital, Seoul, Korea.
Byun
H S
HS
Kim
J J
JJ
D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D018783:Impotence, Vasculogenic / Q000188:drug therapy*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects; D020110:Pinacidil / Q000627:therapeutic use*; D015221:Potassium Channels / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*
D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil