K+ -ATP - Channel Opener as a Potential Treatment for Erectile Dysfunction

Moon, Du Geon; Byun, Hee Suk; Kim, Je Jong

Abstract

PURPOSE: Intracavernous injection of PGE1 or papaverine is widely used in the diagnosis and treatment of erectile dysfunction. However, these drugs have several side effects such as pain, priapism, and fibrotic lesions. In this study, we assessed the effects of pinacidil (a K+ -ATP - channel opener) as an alternative for inducing penile erection.
METHODS
Using a feline model, the magnitude of penile erection caused by pinacicil was compared with that caused by other drugs, namely acetylcholine, PGE1 and L-arginine. The effects of K+ -channel blockers(4-aminopyridine, glibenclamide, and tetraethylammonium; TEA) and pinacidil on the induced erections were investigated.
RESULTS
Intra-arterial injection of pinacicil increased the intracavernous pressure (ICP) in a dose-dependent fashion, and the increase in ICP induced by pinacicil plus acetylcholine, PGE1 or L-arginine was more pronounced than that induced by any of these drugs alone. Furthermore, pinacicil (10(-3)M/mL) effectively reversed the inhibitory effects of the K+-channel blockers on cavernous relaxation induced by acetylcholine, PGE1 or L-arginine (P<0.01). Notably, pinacidil induced cavernous relaxation even in cases refractory to a higher concentration <10(-1) M/mL) of erectics (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 human erectile tissue and clinical testing are required to show whether K+-channel openers can be used in the diagnosis and treatment of erectile dysfunction.