Metformin treatment of angiotensin II hypertensive rats decreased electric field stimulation mediated contraction in corpus cavernosum

The renin-angiotensin system plays an important role in cardiovascular function. However, excessive increases in angiotensin II (AngII) levels are associated with increased vasoconstriction and endothelial dysfunction with concurrent reactive oxygen species (ROS) production and decreased nitric oxide (NO) bioavailability, leading to diseases such as hypertension, atherosclerosis and erectile dysfunction. AMP-activated protein kinase (AMPK) was shown to improve endothelial function, partly through suppression of ROS and increased NO bioavailability. We hypothesized that AMPK activation may protect against increased AngII mediated contraction in corpus covernosum. Corpus cavernosum was isolated from rats that were infused with saline or AngII (65ng/min) and treated with or without the AMPK activator metformin (500mg/kg/day) for 7 days. We observed no difference between the three groups (sham, Ang II and AngII + metformin) in phenylephrine mediated contraction. However, AngII caused an increase in electric field stimulation (EFS) mediated contraction as compared to sham (4.32±0.73 mN vs 2.70±0.52 mN) and treatment with metformin decreased this response, in the absence or presence of L-NAME. From these data, we speculate that metformin may protect against increased AngII mediated contraction through AMPK activation and ROS suppression. Grant support: RO1HL071138