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

Abstract Objective To investigate the possible role of fesoterodine (a competitive muscarinic receptor antagonist) on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Materials And Methods A total of 16 adult male Sprague-Dawley rats were equally divided into control and diabetic g...

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Published in:Urology (Ridgewood, N.J.) N.J.), 2017-09, Vol.107, p.271.e1-271.e7
Main Authors: Yilmaz-Oral, Didem, Bayatli, Nur, Gur, Serap
Format: Article
Language:English
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Summary:Abstract Objective To investigate the possible role of fesoterodine (a competitive muscarinic receptor antagonist) on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Materials And Methods A total of 16 adult male Sprague-Dawley rats were equally divided into control and diabetic group. Diabetes was induced by a single intravenous injection of streptozotocin (25–35mg/kg). In vivo erectile responses were evaluated by the stimulation of cavernosal nerves and repeated after intracavernosal injection of fesoterodine (1µM) in rats. The relaxation responses to fesoterodine were examined incubation with various inhibitors. The relaxant responses of corpus cavernosum (CC) strips were observed in the presence or absence of fesoterodine (10µM). Results Intracavernous administration of fesoterodine restored in vivo erectile response at 5 and 7.5V levels, except for 2.5V in diabetic rats. Basal intracavernosal pressure (5.4±0.9 mmHg) in diabetic rats was markedly increased after given fesoterodine (33.9±7.9 mmHg, 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+ channels blocker) inhibited maximum fesoterodine-induced relaxation by %58. The non-selective K+ channel blocker tetraethylammonium and glibenclamide incubation did not change relaxant response to fesoterodine. The relaxant responses to acetylcholine (10µM), electrical field stimulation (10Hz) and sodium nitroprusside (0.01µM) in diabetic rats were increased after incubation with fesoterodine (10µM). Conclusion Fesoterodine improved erectile function and relaxation of isolated strips of rat CC. The underlying mechanism of fesoterodine is likely due to blocking of L-type calcium channels independent from the NO-cGMP pathway. Further investigations are warranted to fully elucidate the restorative effects of fesoterodine on overactive bladder-induced diabetic ED.
ISSN:0090-4295
1527-9995
DOI:10.1016/j.urology.2017.05.041