ORIGINAL RESEARCH-BASIC SCIENCE
Metformin Treatment Improves Erectile Function in an Angiotensin II Model of Erectile Dysfunction
Article first published online: 24 JUL 2013
© 2013 International Society for Sexual Medicine
The Journal of Sexual Medicine
Volume 10, Issue 9, pages 2154–2164, September 2013
How to Cite
Labazi, H., Wynne, B. M., Tostes, R. and Webb, R. C. (2013), Metformin Treatment Improves Erectile Function in an Angiotensin II Model of Erectile Dysfunction. Journal of Sexual Medicine, 10: 2154–2164. doi: 10.1111/jsm.12245
- Issue published online: 3 SEP 2013
- Article first published online: 24 JUL 2013
- National Institutes of Health. Grant Numbers: NIH - HL71138, DK83685
- Society for Women’s Health Research
- Sexual Medicine Society of North America Scholars in Sexuality Research Grant
- Angiotensin II;
- Erectile Dysfunction;
- Corpus Cavernosum;
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.
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.
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.
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.
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.