title: Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion.
abstract: OBJECTIVE
  Recent studies have demonstrated that perivascular adipose tissue (PVAT) releases vascular relaxation factor(s). In this study, we examined if PVAT releases other vasoactive factors in response to perivascular nerve activation by electrical field stimulation (EFS).
  
  
  RESULTS
  In Wistar-Kyoto rats, rings of superior mesenteric artery (MA) with intact PVAT (PVAT (+)) showed a greater contractile response to EFS than rings with PVAT removed (PVAT (-)). Superoxide dismutase (SOD) reduced the contractile response to EFS more in PVAT (+) MA than in PVAT (-) MA. Inhibitors of NAD(P)H oxidase and cyclooxygenase exerted a greater inhibition on EFS-induced contraction in PVAT (+) MA than in PVAT (-) MA. Inhibitors of tyrosine kinase (tyrphostin A25) and MAPK/ERK (U 0126) attenuated EFS-induced contraction in PVAT (+) MA in a concentration-related manner, while inactive forms of these inhibitors (tyrphostin A1 and U 0124) did not inhibit the response. Exogenous superoxide augmented the contractile response to EFS and to phenylephrine in PVAT (-) MA, and this augmentation was blunted by inhibition of tyrosine kinase and MAPK/ERK. EFS increased superoxide generation in isolated PVAT and PVAT (+)/(-) MA, which was attenuated by NAD(P)H oxidase inhibition. RT-PCR showed the mRNA expression of p(67phox) subunit of NAD(P)H oxidase and immunohistochemical staining confirmed its localization in the adipocytes of PVAT.
  
  
  CONCLUSIONS
  These results show that PVAT enhances the arterial contractile response to perivascular nerve stimulation through the production of superoxide mediated by NAD(P)H oxidase, and that this enhancement involves activation of tyrosine kinase and MAPK/ERK pathway.
authors.affiliation: Smooth Muscle Research Program and Department of Anaesthesia, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. gaoyu@mcmaster.ca
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Gao
authors.forename: Kumiko
authors.initials: K
authors.lastname: Takemori
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Su
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: An
authors.forename: Chao
authors.initials: C
authors.lastname: Lu
authors.forename: Arya M
authors.initials: AM
authors.lastname: Sharma
authors.forename: Robert M K W
authors.initials: RM
authors.lastname: Lee
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000494:pharmacology; D010656:Phenylephrine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology*; D020032:Tyrphostins / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D002070:Butadienes; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D020032:Tyrphostins; C113580:U 0126; D013481:Superoxides; D000804:Angiotensin II; C079836:tyrphostin 25; D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D019331:NG-Nitroarginine Methyl Ester