A POSSIBLE MECHANISM FOR ALTERATION OF HUMAN ERECTILE FUNCTION BY DIGOXIN - INHIBITION OF CORPUS CAVERNOSUM SODIUM POTASSIUM ADENOSINE-TRIPHOSPHATASE ACTIVITY/

Purpose: Digoxin use has long been recognized to affect adversely male sexual function but the underlying mechanism is poorly understood, Di goxin is a known inhibitor of sodium/potassium adenosine triphosphatas e (sodium pump), a plasma membrane enzyme that has a role in the regul ation of smooth muscle tone. We investigated the effects of digoxin on human corpus cavernosum smooth muscle contractility and overall erect ile function. Materials and Methods: In human corporeal smooth muscle strips the in vitro effects of digoxin were assessed on sodium pump ac tivity as measured by digoxin inhibitable uptake of (86)rubidium, basa l tone and endothelium dependent, neurogenic and nitric oxide donor in duced relaxation. An in vivo prospective double-blind, placebo control led, crossover, 4-period investigation was performed in 6 healthy male volunteers. The effects of digoxin on serum hormones, erectile functi on questionnaire, visual sexual stimulation and nocturnal penile tumes cence were recorded, Results: In vitro digoxin caused concentration de pendent inhibition of (86)rubidium uptake (half maximum effect at 0.01 mu M.) and contraction of corporeal smooth muscle (half maximum effec t at 0.8 mu M.). Therapeutic concentrations of digoxin (2 nM.) also in hibited relaxation induced by acetylcholine and electrical field stimu lation, which release nitric oxide from corpus cavernosum endothelial cells and nonadrenergic noncholinergic nerves, respectively. In vivo d igoxin diminished penile rigidity during visual sexual stimulation and nocturnal penile tumescence testing compared to placebo without influ encing libido or serum testosterone, estrogen or luteinizing hormone l evels. Conclusions: Digoxin associated alteration of human erectile fu nction may be explained, in part, by inhibition of corporeal smooth mu scle sodium pump activity, which promotes contraction and impedes nitr ic oxide induced relaxation. Such findings suggest therapeutic use of digoxin for treatment of recurrent priapism states.