Mirabegron elicits recovery of erectile function in a rat model of streptozotocin-induced diabetes
Kaya Sezginer, E1; Yilmaz Oral, D2; Askin, D2; Koroglu, G2; Gur, S2
1: Department of Biochemistry, Faculty of Pharmacy, Ankara University, Turkey; 2: Department of Pharmacology, Faculty of Pharmacy, Ankara University, Turkey
Objectives: Erectile dysfunction (ED) is a growing problem among men with diabetes. Phosphodiesterase type 5 inhibitors (PDE5i) are not effective in the management of diabetes-associated ED. Mirabegron, a selective β3-adrenoceptor agonist, has been approved for the treatment of overactive bladder. This study is focused on the possible beneficial effect of intracavernosal injection of mirabegron on ED in streptozotocin-induced diabetic rats.
Materials and Methods: Adult Sprague-Dawley (n=20) rats were equally divided into two groups: control and diabetic rats subjected to streptozotocin (45 mg/kg, intraperitoneal). In vivo erectile responses were also repeated after intracavernosal injection of mirabegron (dose of 0.4 mg/kg). The relaxant responses of corpus cavernosum (CC) strips were evaluated in the presence or absence of mirabegron (10 μM). Expression and localization of β3-adrenoceptors in penile tissue were determined by Western blot analysis and immunohistochemistry.
Results: Diabetic rats demonstrated significantly decreased ratio of intracavernosal pressure to mean arterial
pressure (0.17± 0.02; P < .001) and total intracavernosal pressure (2057 ± 199 mmHg; P < .001) which were restored by intracavernosal administration of mirabegron (0.75± 0.01; 3888 ± 295 mmHg). The basal intracavernosal pressure in diabetic rats was markedly increased after mirabegron. In in vitro studies, the nitrergic relaxation response to electrical field stimulation (10 Hz) in diabetic CC was enhanced almost 7-fold after the presence of mirabegron. Mirabegron increased sodium nitroprusside-induced (10nM) relaxation in CC of diabetic rats. The relaxant response to sildenafil (1µM) in the diabetic group was lower than the control group, which was augmented after incubation with mirabegron. The protein expression and localization of β3-adrenoceptors in the CC did not differ between diabetic and control rats.
Conclusions: We firstly indicated that the intracavernosal administration of mirabegron improved recovery of erectile function and neurogenic relaxation of CC in diabetic rats. Further studies should focus on expanding combinations of mirabegron and PDE5i that may be useful for improving clinical outcomes in diabetic men with ED.
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