Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction

Hicham Labazi, Brandi M. Wynne, Rita Tostes, R. Clinton Webb

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

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 (70ng/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.
Original languageEnglish
Pages (from-to)2154-2164
Number of pages11
JournalThe Journal of Sexual Medicine
Volume10
Issue number9
DOIs
Publication statusPublished - 1 Sept 2013

Keywords

  • angiotensin II
  • erectile dysfunction
  • corpus cavernosum
  • hypertension
  • metformin
  • eNOS

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