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J Sex Med. 2013 Sep;10(9):2154-64. doi: 10.1111/jsm.12245. Epub 2013 Jul 24.

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

Author information

1
Georgia Health Sciences University, Physiology Department, Augusta, GA, USA.

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 (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.

KEYWORDS:

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

PMID:
23889981
PMCID:
PMC4429591
DOI:
10.1111/jsm.12245
[Indexed for MEDLINE]
Free PMC Article

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