Fábio H Silva1, Eduardo C Alexandre2, Fabiano B Calmasini2, Marina C Calixto2, Edson Antunes2. 1. Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil. Electronic address: fabiohsilva87@gmail.com. 2. Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.
Abstract
OBJECTIVE: To evaluate the effects of treatment with metformin on a murine model of obesity-associated erectile dysfunction. MATERIAL AND METHODS: C57BL/6 male mice were fed for 10 weeks with standard chow or high-fat diet. Lean and obese mice were treated with the insulin sensitizer metformin (300 mg/kg/day, 2 weeks). Intracavernosal pressure (ICP) and in vitro corpus cavernosum (CC) relaxations to both acetylcholine and electrical field stimulation, as well as phenylephrine-induced contractions, were obtained. Levels of cyclic guanosine monophosphate in CC were detected by enzyme immunoassay. RESULTS: High-fat-fed mice exhibited higher body weight and insulin resistance. Cavernous nerve stimulation caused frequency-dependent ICP increases, which were significantly lower in obese compared with lean mice (P <.05). Two-week therapy with metformin reversed the decreased ICP in obese group. The maximal response to acetylcholine in CC was 35% lower (P <.05) in the obese compared to the lean group, which were restored by metformin treatment. Likewise, the impaired electrical field stimulation-induced CC relaxations in obese mice were also partly restored by metformin. Contractile responses to phenylephrine were significantly greater (P <.05) in obese compared to lean mice, which were fully restored by metformin. Basal and stimulated cyclic guanosine monophosphate productions in the erectile tissues were significantly lower (P <.05) in the obese group, an effect fully restored by metformin. CONCLUSION: Treatment with metformin restored the erectile function in obese mice, through improvement of in vitro endothelial and nitrergic cavernosal relaxations. Therefore, use of metformin may be a good pharmacologic approach to treat insulin resistance-associated erectile dysfunction.
OBJECTIVE: To evaluate the effects of treatment with metformin on a murine model of obesity-associated erectile dysfunction. MATERIAL AND METHODS: C57BL/6 male mice were fed for 10 weeks with standard chow or high-fat diet. Lean and obesemice were treated with the insulin sensitizer metformin (300 mg/kg/day, 2 weeks). Intracavernosal pressure (ICP) and in vitro corpus cavernosum (CC) relaxations to both acetylcholine and electrical field stimulation, as well as phenylephrine-induced contractions, were obtained. Levels of cyclic guanosine monophosphate in CC were detected by enzyme immunoassay. RESULTS: High-fat-fed mice exhibited higher body weight and insulin resistance. Cavernous nerve stimulation caused frequency-dependent ICP increases, which were significantly lower in obese compared with lean mice (P <.05). Two-week therapy with metformin reversed the decreased ICP in obese group. The maximal response to acetylcholine in CC was 35% lower (P <.05) in the obese compared to the lean group, which were restored by metformin treatment. Likewise, the impaired electrical field stimulation-induced CC relaxations in obesemice were also partly restored by metformin. Contractile responses to phenylephrine were significantly greater (P <.05) in obese compared to lean mice, which were fully restored by metformin. Basal and stimulated cyclic guanosine monophosphate productions in the erectile tissues were significantly lower (P <.05) in the obese group, an effect fully restored by metformin. CONCLUSION: Treatment with metformin restored the erectile function in obesemice, through improvement of in vitro endothelial and nitrergic cavernosal relaxations. Therefore, use of metformin may be a good pharmacologic approach to treat insulin resistance-associated erectile dysfunction.
Authors: Fernanda Priviero; Fabiano Calmasini; Vanessa Dela Justina; Camilla F Wenceslau; Cameron G McCarthy; R Clinton Webb Journal: J Sex Med Date: 2021-03-16 Impact factor: 3.802
Authors: Fernanda B M Priviero; Haroldo A F Toque; Kenia Pedrosa Nunes; Denise G Priolli; Cleber E Teixeira; R Clinton Webb Journal: PLoS One Date: 2016-05-26 Impact factor: 3.240