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 journalArticle

19 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. Labazi H, Wynne BM, Tostes R, and Webb RC. Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction. J Sex Med 2013;10:2154-2164.

Original languageEnglish (US)
Pages (from-to)2154-2164
Number of pages11
JournalJournal of Sexual Medicine
Volume10
Issue number9
DOIs
StatePublished - Jan 1 2013

Fingerprint

Metformin
Erectile Dysfunction
Angiotensin II
Phosphorylation
Proteins
AMP-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Nitric Oxide Synthase
Smooth Muscle
Sprague Dawley Rats
Outcome Assessment (Health Care)
Hypertension
Pressure

Keywords

  • Angiotensin II
  • Corpus Cavernosum
  • Erectile Dysfunction
  • Hypertension
  • Metformin
  • eNOS

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Urology

Cite this

Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction. / Labazi, Hicham; Wynne, Brandi M.; Tostes, Rita; Webb, R Clinton.

In: Journal of Sexual Medicine, Vol. 10, No. 9, 01.01.2013, p. 2154-2164.

Research output: Contribution to journalArticle

Labazi, Hicham ; Wynne, Brandi M. ; Tostes, Rita ; Webb, R Clinton. / Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction. In: Journal of Sexual Medicine. 2013 ; Vol. 10, No. 9. pp. 2154-2164.
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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. Labazi H, Wynne BM, Tostes R, and Webb RC. Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction. J Sex Med 2013;10:2154-2164.",
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AB - 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. Labazi H, Wynne BM, Tostes R, and Webb RC. Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction. J Sex Med 2013;10:2154-2164.

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