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Prolonged treatment with angiotensin 1-7 improves endothelial function in diet-induced obesity
Journal article   Open access   Peer reviewed

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

Andreas M Beyer, Deng-Fu Guo and Kamal Rahmouni
Journal of hypertension, Vol.31(4), pp.730-738
04/2013
DOI: 10.1097/HJH.0b013e32835ecbe5
PMCID: PMC5684878
PMID: 23425706
url
http://doi.org/10.1097/HJH.0b013e32835ecbe5View
Open Access

Abstract

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. 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. 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 (p22(phox) and p47(phox)) and plasma TBARS associated with DIO mice. In contrast, treatment with Ang 1-7 did not normalize the altered contractions associated with DIO mice. Our data demonstrate a novel role for Ang 1-7 in improving obesity-associated endothelial dysfunction.
Mice, Inbred C57BL Peptide Fragments - administration & dosage Angiotensin I - administration & dosage Endothelium, Vascular - physiopathology Endothelium, Vascular - drug effects Male Obesity - physiopathology Peptide Fragments - pharmacology DNA Primers Reverse Transcriptase Polymerase Chain Reaction Animals Diet Base Sequence Obesity - etiology Angiotensin I - pharmacology Mice

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