The Beneficial Effect of Fesoterodine, a Competitive Muscarinic Receptor Antagonist on Erectile Dysfunction in Streptozotocin-induced Diabetic Rats

Abstract

To investigate the possible role of fesoterodine (a competitive muscarinic receptor antagonist) on erectile dysfunction in streptozotocin-induced diabetic rats. A total of 16 adult male Sprague-Dawley rats were equally divided into control and diabetic groups. Diabetes was induced by a single intravenous injection of streptozotocin (25-35 mg/kg). In vivo erectile responses were evaluated by the stimulation of cavernosal nerves, and measurements were repeated after the intracavernosal injection of fesoterodine (1 µM) in rats. The relaxation responses to fesoterodine were examined via incubation with various inhibitors. The relaxant responses of corpus cavernosum (CC) strips were observed in the presence or the absence of fesoterodine (10 µM). Intracavernous administration of fesoterodine restored in vivo erectile response at 5.0- and 7.5-V levels, except for 2.5 V in diabetic rats. Basal intracavernosal pressure (5.4 ± 0.9 mm Hg) in diabetic rats was markedly increased after injection of fesoterodine (33.9 ± 7.9 mm Hg, P <.001). In bath studies, fesoterodine resulted in a relaxation of CC in a concentration-dependent manner, which was reduced in diabetic rats. Nifedipine (l-type Ca2+ channel blocker) inhibited maximum fesoterodine-induced relaxation by 58%. The nonselective K+ channel blocker tetraethylammonium and glibenclamide incubation did not change the relaxant response to fesoterodine. The relaxant responses to acetylcholine (10 µM), electrical field stimulation (10 Hz), and sodium nitroprusside (0.01 µM) in diabetic rats were increased after incubation with fesoterodine (10 µM). Fesoterodine improved erectile function and relaxation of isolated strips of rat CC. The underlying mechanism of fesoterodine is likely due to the blocking of l-type calcium channels independent of the nitric oxide-cyclic guanosine monophosphate pathway. Further investigations are warranted to fully elucidate the restorative effects of fesoterodine on overactive bladder-induced diabetic erectile dysfunction.