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Prolonged treatment with angiotensin 1–7 improves endothelial function in diet-induced obesity

Beyer, Andreas M.a; Guo, Deng-Fub; Rahmouni, Kamala,b

doi: 10.1097/HJH.0b013e32835ecbe5
ORIGINAL PAPERS: Renin-angiotensin system

Objective: The renin–angiotensin system peptides are critically involved in the regulation of endothelial function with important pathological implications. Angiotensin (Ang) 1–7 has many beneficial effects in the vasculature that modulate the cardiovascular risk. Here, we tested the hypothesis that Ang 1–7 has a protective role against the endothelial defects associated with diet-induced obesity (DIO) in mice.

Methods: Ang 1–7 (with or without Ang II) was delivered subcutaneously for 4 weeks using osmotic minipumps. Vascular studies were performed using aortic rings. Arterial pressure and heart rate were measured in separate cohorts of mice by telemetry.

Results: First, we examined whether chronic administration of Ang 1–7 improves the vascular dysfunctions caused by Ang II. Subcutaneous coinfusion of Ang 1–7 significantly attenuates Ang II-induced endothelial dysfunctions. In addition, DIO mice have significant impairment in the endothelium-dependent relaxation. The contractile responses induced by various stimuli, including serotonin and endothelin-1, were differentially altered in DIO mice. Notably, DIO mice treated with Ang 1–7 for 4 weeks displayed significant improvement in the endothelial function as indicated by the increased acetylcholine-induced relaxation. Consistent with this, chronic treatment with Ang 1–7 reversed the increased aortic expression of NAD(P)H oxidase subunits (p22phox and p47phox) and plasma TBARS associated with DIO mice. In contrast, treatment with Ang 1–7 did not normalize the altered contractions associated with DIO mice.

Conclusion: Our data demonstrate a novel role for Ang 1–7 in improving obesity-associated endothelial dysfunction.

aDepartment of Internal Medicine

bDepartment of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA

Correspondence to Kamal Rahmouni, PhD, University of Iowa Carver College of Medicine, 3135C MERF, Iowa City, IA52242, USA. Tel: +1 319 353 5256; fax: +1 319 353 5350; e-mail: kamal-rahmouni@uiowa.edu

Abbreviations: 5-HT, serotonin; ACE, angiotensin-converting enzyme; ACh, acetylcholine; Ang, angiotensin; ET-1, endothelin; DIO, diet-induced obesity; Pgf, prostaglandin F; RAS, renin–angiotensin system; SNP, sodium nitroprusside; TBARS, thiobarbituric acid-reactive substances

Received 1 November, 2012

Accepted 9 January, 2013

© 2013 Lippincott Williams & Wilkins, Inc.