Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction.
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.
['Labazi|Hicham|H|', 'Wynne|Brandi M|BM|', 'Tostes|Rita|R|', 'Webb|R Clinton|RC|']
D055372:AMP-Activated Protein Kinases D000804:Angiotensin II D000818:Animals D000959:Antihypertensive Agents D062186:Arterial Pressure D004195:Disease Models, Animal D007172:Erectile Dysfunction D006801:Humans D006973:Hypertension D008297:Male D008687:Metformin D019950:Mitogen-Activated Protein Kinase 1 D048052:Mitogen-Activated Protein Kinase 3 D052248:Nitric Oxide Synthase Type I D052250:Nitric Oxide Synthase Type III D010410:Penile Erection D010413:Penis D010766:Phosphorylation D051381:Rats D017207:Rats, Sprague-Dawley D015398:Signal Transduction
Metformin Angiotensin II Erectile Dysfunction Hypertension Corpus Cavernosum eNOS