title: Modulation of vein function by perivascular adipose tissue.
abstract: Although a number of studies have shown that perivascular adipose tissue (PVAT) attenuates arterial contraction through the release of perivascular-derived relaxation factors (PVRF), the role of PVAT in modulating venous function and its mechanism(s) remained unknown. Here we examined the role of PVAT in the modulation of vascular function in the inferior vena cava. Venous rings from male Wistar rats were prepared with both endothelium and PVAT intact, with either PVAT or endothelium removed, or with both endothelium and PVAT removed for functional studies. Contractile response to phenylephrine, U 46619, or 5-hydroxytryptamine was significantly attenuated in PVAT+ as compared with PVAT- veins. PVAT- vessels with intact endothelium (E+) pre-contracted with phenylephrine showed a concentration-dependent relaxation response to angiotensin 1-7 [Ang-(1-7)], and this response was abolished by the removal of endothelium, and by Ang-(1-7) (Mas) receptor antagonists D-Ala-Ang-(1-7) (A779) or D-Pro(7)-Ang-(1-7). Donor solution incubated with a PVAT+ ring induced a relaxation response in the E+ recipient vessel but not in E- recipient vessel. The use of specific channel blockers and enzyme inhibitors showed that Ang-(1-7) is a transferable PVRF that induces endothelium-dependent relaxation through NO release and activation of voltage-dependent potassium (K(+)) channels (K(v)) channels. We conclude that venous PVAT attenuates agonist-induced contraction by releasing Ang-(1-7), which causes relaxation of smooth muscle through endothelial NO release and activation of K(v) channels.
authors.affiliation: Smooth Muscle Research Program and Department of Anesthesia, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Chao
authors.initials: C
authors.lastname: Lu
authors.forename: Ashley X
authors.initials: AX
authors.lastname: Zhao
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Gao
authors.forename: Robert M K W
authors.initials: RM
authors.lastname: Lee
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014682:Vena Cava, Inferior / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D010446:Peptide Fragments; D015221:Potassium Channels; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D010656:Phenylephrine; D009569:Nitric Oxide; D000803:Angiotensin I; C118790:angiotensin I (1-7)