title: Endothelium-dependent relaxation factor released by perivascular adipose tissue.
abstract: OBJECTIVE
  Recent studies have demonstrated that perivascular adipose tissue (PVAT) releases vascular relaxation factor(s), but the identity of this relaxation factor remains unknown. Here, we examined if angiotensin 1-7 [Ang-(1-7)] is one of the relaxation factors released by PVAT.
  
  
  METHODS
  Morphological and functional methods were used to study aorta from adult Wistar rats.
  
  
  RESULTS
  Immunohistochemical staining showed abundant presence of Ang-(1-7) in aortic PVAT. In vessels with PVAT removed but intact endothelium (PVAT - E+), contraction induced by phenylephrine was attenuated by preincubation with Ang-(1-7). PVAT - E+ vessels precontracted with phenylephrine showed a concentration-dependent relaxation response to Ang-(1-7), and this response was abolished by the removal of endothelium. Relaxation response induced by Ang-(1-7) was also prevented by Ang-(1-7) receptor (Mas) antagonist (A779), nitric oxide synthase inhibitor, and nitric oxide scavenger. Ang-(1-7) did not cause a relaxation response in aorta precontracted with KCl, and the relaxation response to Ang-(1-7) was also blocked by calcium-dependent potassium (K(Ca)) channel blockers. Incubation of PVAT + E+ vessels with A779 or angiotensin-converting enzyme 2 inhibitor DX600 or angiotensin-converting enzyme inhibitor enalaprilat increased the contraction induced by phenylephrine. Transfer of donor solution incubated with PVAT + E+ vessel to recipient PVAT - E+ vessel caused a relaxation response. This relaxation response was abolished when donor vessels were incubated with DX600 or enalaprilat or when recipient vessels were incubated with A779.
  
  
  CONCLUSIONS
  Ang-(1-7) released by PVAT acts on the endothelium to cause the release of nitric oxide, and nitric oxide acts as a hyperpolarizing factor through K(Ca) channels to cause relaxation of the blood vessel.
authors.affiliation: Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada. rmkwlee@mcmaster.ca
authors.forename: Robert M K W
authors.initials: RM
authors.lastname: Lee
authors.forename: Chao
authors.initials: C
authors.lastname: Lu
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Su
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Gao
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000803:Angiotensin I / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D045462:Endothelium-Dependent Relaxing Factors / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D010446:Peptide Fragments / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013841:Thiazepines / Q000494:pharmacology
chemical_list: C092006:7-Ala-angiotensin (1-7); D000806:Angiotensin-Converting Enzyme Inhibitors; D045462:Endothelium-Dependent Relaxing Factors; D010446:Peptide Fragments; D015221:Potassium Channels; D011725:Pyridines; D013841:Thiazepines; D000804:Angiotensin II; C106266:omapatrilat; D000803:Angiotensin I; C118790:angiotensin I (1-7)