Metformin Reverses the Effects of Angiotensin 2 in Human Mammary Arteries by Modulating the Expression of Nitric Oxide Synthases

Author:

Merce Adrian12,Buriman Darius G.2,Lascu Ana34,Bînă Anca M.34,Feier Horea B.2,Petrescu Lucian14,Borza Claudia34,Sturza Adrian34,Muntean Danina M.34,Crețu Octavian M.56

Affiliation:

1. Doctoral School Medicine-Pharmacy ,

2. Cardiovascular Surgery - Institute for Cardiovascular Diseases ,

3. Department of Functional Sciences - Pathophysiology ,

4. Centre for Translational Research and Systems Medicine ,

5. Department of Surgery - Surgical Semiotics I ,

6. Centre for Hepato-Biliary and Pancreatic Surgery,“Victor Babeș” University of Medicine and Pharmacy , Timișoara Romania , Eftimie Murgu Sq. no. 2, 300041 Timișoara, RO

Abstract

Abstract Angiotensin 2 impairs vascular function by activation of reactive oxygen species (ROS) production and development of endothelial dysfunction. Metformin, the first-line therapeutic agent for type 2 diabetes mellitus, has vascular protective properties, beyond its glucose lowering effects. The aim of the present study was to investigate the interaction between metformin and angiotensin 2 in human internal mammary arteries harvested from patients with coronary heart disease undergoing revascularization procedure, by evaluation of vascular function, reactive oxygen species (ROS) production and the gene expression of nitric oxide (NO) synthases (endothelial – eNOS, neuronal – nNOS and inducible – iNOS). To this aim, vascular samples were incubated with angiotensin 2 (Ang2, 12 h) with/without metformin (Metf, 10 μM) and used for ROS measurement (FOX assay), vascular reactivity in organ bath (contractility to phenylephrine, relaxation to acetylcholine, contractility to NG-nitro-L-arginine methyl ester/L-NAME) and RTPCT studies. Acute incubation of the vascular rings with Ang2 impaired vascular reactivity (increase contractility, decrease relaxation), increased ROS production, supressed eNOS/nNOS and increased iNOS mRNA expression. Ex vivo incubation with metformin at a clinically relevant concentration reversed all these effects. These data suggest that Metformin might be useful in alleviating endothelial dysfunction by improving the endothelial-dependent relaxation and mitigating oxidative stress in clinical setting associated with cardiovascular disease regardless the presence of impaired glucose metabolism.

Publisher

Walter de Gruyter GmbH

Subject

General Medicine

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