title: Cyclooxygenase inhibition improves endothelial vasomotor dysfunction of visceral adipose arterioles in human obesity.
abstract: OBJECTIVE
  The purpose of this study was to determine whether cyclooxygenase inhibition improves vascular dysfunction of adipose microvessels from obese humans.
  
  
  METHODS
  In 20 obese subjects (age 37 ± 12 years, BMI 47 ± 8 kg/m²), subcutaneous and visceral fat were collected during bariatric surgery and characterized for adipose depot-specific gene expression, endothelial cell phenotype, and microvascular function. Vasomotor function was assessed in response to endothelium-dependent agonists using videomicroscopy of small arterioles from fat.
  
  
  RESULTS
  Arterioles from visceral fat exhibited impaired endothelium-dependent, acetylcholine-mediated vasodilation, compared to the subcutaneous depot (P < 0.001). Expression of mRNA transcripts relevant to the cyclooxygenase pathway was upregulated in visceral compared to subcutaneous fat. Pharmacological inhibition of cyclooxygenase with indomethacin improved endothelium-dependent vasodilator function of arterioles from visceral fat by twofold (P = 0.01), whereas indomethacin had no effect in the subcutaneous depot. Indomethacin increased activation via serine-1177 phosphorylation of endothelial nitric oxide synthase in response to acetylcholine in endothelial cells from visceral fat. Inhibition of endothelial nitric oxide synthase with N(ω)-nitro-L-arginine methyl ester abrogated the effects of cyclooxygenase-inhibition suggesting that vascular actions of indomethacin were related to increased nitric oxide bioavailability.
  
  
  CONCLUSIONS
  Our findings suggest that cyclooxygenase-mediated vasoconstrictor prostanoids partly contribute to endothelial dysfunction of visceral adipose arterioles in human obesity.
authors: Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, USA.
authors: Melissa G
authors: MG
authors: Farb
authors: Stephanie
authors: S
authors: Tiwari
authors: Shakun
authors: S
authors: Karki
authors: Doan T M
authors: DT
authors: Ngo
authors: Brian
authors: B
authors: Carmine
authors: Donald T
authors: DT
authors: Hess
authors: Maria A
authors: MA
authors: Zuriaga
authors: Kenneth
authors: K
authors: Walsh
authors: Jessica L
authors: JL
authors: Fetterman
authors: Naomi M
authors: NM
authors: Hamburg
authors: Joseph A
authors: JA
authors: Vita
authors: Caroline M
authors: CM
authors: Apovian
authors: Noyan
authors: N
authors: Gokce
mesh_terms: D000328:Adult; D001160:Arterioles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015992:Body Mass Index; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050152:Intra-Abdominal Fat / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018715:Microscopy, Video; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D050507:Subcutaneous Fat, Abdominal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D046509:Tissue Culture Techniques; D014661:Vasoconstriction / Q000187:drug effects*; D014666:Vasomotor System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat
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