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Prolonged treatment with angiotensin 1-7 improves endothelial function in diet-induced obesity. J Hypertens 2013 Apr;31(4):730-8

Date

02/22/2013

Pubmed ID

23425706

Pubmed Central ID

PMC5684878

DOI

10.1097/HJH.0b013e32835ecbe5

Scopus ID

2-s2.0-84875214685 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

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 (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.

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

Author List

Beyer AM, Guo DF, Rahmouni K

Author

Andreas M. Beyer PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Angiotensin I
Animals
Base Sequence
DNA Primers
Diet
Endothelium, Vascular
Male
Mice
Mice, Inbred C57BL
Obesity
Peptide Fragments
Reverse Transcriptase Polymerase Chain Reaction