title: Prolonged treatment with angiotensin 1-7 improves endothelial function in diet-induced obesity.
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.
  
  
  CONCLUSIONS
  Our data demonstrate a novel role for Ang 1-7 in improving obesity-associated endothelial dysfunction.
authors: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Andreas M
authors: AM
authors: Beyer
authors: Deng-Fu
authors: DF
authors: Guo
authors: Kamal
authors: K
authors: Rahmouni
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004032:Diet; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D010446:Peptide Fragments; D000803:Angiotensin I; C118790:angiotensin I (1-7)