Prolonged treatment with angiotensin 1-7 improves endothelial function in diet-induced obesity. J Hypertens 2013 Apr;31(4):730-8
Date
02/22/2013Pubmed ID
23425706Pubmed Central ID
PMC5684878DOI
10.1097/HJH.0b013e32835ecbe5Scopus ID
2-s2.0-84875214685 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
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 KAuthor
Andreas M. Beyer PhD Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin IAnimals
Base Sequence
DNA Primers
Diet
Endothelium, Vascular
Male
Mice
Mice, Inbred C57BL
Obesity
Peptide Fragments
Reverse Transcriptase Polymerase Chain Reaction