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Endothelium-dependent relaxation factor released by perivascular adipose tissue

Lee, Robert MKW; Lu, Chao; Su, Li-Ying; Gao, Yu-Jing

doi: 10.1097/HJH.0b013e328324ed86
Original papers: Pathophysiological aspects

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.

Method 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 (KCa) 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.

Conclusion 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 KCa channels to cause relaxation of the blood vessel.

Department of Anesthesia, Smooth Muscle Research Program, McMaster University, Hamilton, Ontario, Canada

Received 11 September, 2008

Revised 13 November, 2008

Accepted 2 December, 2008

Correspondence to Dr Robert M.K.W. Lee, Professor, Department of Anesthesia (HSC-2U3), McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5 Tel: +1 905 521 2100 x75177; fax: +1 905 523 1224; e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.