INTRODUCTION: Increased angiotensin II (AngII) levels cause hypertension, which is a major risk factor for erectile dysfunction (ED). Studies have demonstrated that increased AngII levels in penile tissue are associated with ED. A recent study showed that metformin treatment restored nitric oxide synthase (NOS) protein expression in penile tissue in obese rats; however, whether metformin treatment can be beneficial and restore erectile function in a model of ED has not yet been established. AIM: The goal of this study was to test the hypothesis that AngII induces ED by means of increased corpus cavernosum contraction, and that metformin treatment will reverse ED in AngII-treated rats. METHODS: Male Sprague-Dawley rats were implanted with mini-osmotic pumps containing saline or AngII (70 ng/minute, 28 days). Animals were then treated with metformin or vehicle during the last week of AngII infusion. MAIN OUTCOME MEASURES: Intracavernosal pressure; corpus cavernosum contraction and relaxation; nNOS protein expression; extracellular signal-regulated kinase (ERK1/2), AMP-activated protein kinase (AMPK), and eNOS protein expression and phosphorylation. RESULTS: AngII-induced ED was accompanied with an increase in corpus cavernosum contractility, decreased nitrergic relaxation, and increased ERK1/2 phosphorylation. Metformin treatment improved erectile function in the AngII-treated rats by reversing the increased contraction and decreased relaxation. Metformin treatment also resulted in an increase in eNOS phosphorylation at ser1177. CONCLUSIONS: Metformin treatment increased eNOS phosphorylation and improved erectile function in AngII hypertensive rats by reestablishing normal cavernosal smooth muscle tone.
INTRODUCTION: Increased angiotensin II (AngII) levels cause hypertension, which is a major risk factor for erectile dysfunction (ED). Studies have demonstrated that increased AngII levels in penile tissue are associated with ED. A recent study showed that metformin treatment restored nitric oxide synthase (NOS) protein expression in penile tissue in obeserats; however, whether metformin treatment can be beneficial and restore erectile function in a model of ED has not yet been established. AIM: The goal of this study was to test the hypothesis that AngII induces ED by means of increased corpus cavernosum contraction, and that metformin treatment will reverse ED in AngII-treated rats. METHODS: Male Sprague-Dawley rats were implanted with mini-osmotic pumps containing saline or AngII (70 ng/minute, 28 days). Animals were then treated with metformin or vehicle during the last week of AngII infusion. MAIN OUTCOME MEASURES: Intracavernosal pressure; corpus cavernosum contraction and relaxation; nNOS protein expression; extracellular signal-regulated kinase (ERK1/2), AMP-activated protein kinase (AMPK), and eNOS protein expression and phosphorylation. RESULTS:AngII-induced ED was accompanied with an increase in corpus cavernosum contractility, decreased nitrergic relaxation, and increased ERK1/2 phosphorylation. Metformin treatment improved erectile function in the AngII-treated rats by reversing the increased contraction and decreased relaxation. Metformin treatment also resulted in an increase in eNOS phosphorylation at ser1177. CONCLUSIONS:Metformin treatment increased eNOS phosphorylation and improved erectile function in AngIIhypertensiverats by reestablishing normal cavernosal smooth muscle tone.
Authors: Fernando S Carneiro; Kênia P Nunes; Fernanda R C Giachini; Victor V Lima; Zidonia N Carneiro; Edson F Nogueira; Romulo Leite; Adviye Ergul; William E Rainey; R Clinton Webb; Rita C Tostes Journal: J Sex Med Date: 2008-09-24 Impact factor: 3.802
Authors: Fernando S Carneiro; Fernanda R C Giachini; Victor V Lima; Zidonia N Carneiro; Kênia P Nunes; Adviye Ergul; Romulo Leite; Rita C Tostes; R Clinton Webb Journal: Can J Physiol Pharmacol Date: 2008-06 Impact factor: 2.273