Obesity (Silver Spring, Md.), 2014-02, Vol.22 (2), p.349-355
2014
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- Autor(en) / Beteiligte
- Titel
- Cyclooxygenase inhibition improves endothelial vasomotor dysfunction of visceral adipose arterioles in human obesity
- Ist Teil von
- Obesity (Silver Spring, Md.), 2014-02, Vol.22 (2), p.349-355
- Ort / Verlag
- United States: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Objective The purpose of this study was to determine whether cyclooxygenase inhibition improves vascular dysfunction of adipose microvessels from obese humans. Design and 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 Nω‐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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1930-7381eISSN: 1930-739XDOI: 10.1002/oby.20505Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3766380
- Format
- –
- Schlagworte
- Adult, Arterioles - drug effects, Arterioles - metabolism, Arterioles - pathology, Arterioles - physiopathology, Body Mass Index, Cells, Cultured, Cyclooxygenase Inhibitors - pharmacology, Endothelium, Vascular - drug effects, Endothelium, Vascular - metabolism, Endothelium, Vascular - pathology, Endothelium, Vascular - physiopathology, Enzyme Activation - drug effects, Enzyme Inhibitors - pharmacology, Female, Gene Expression Regulation - drug effects, Humans, Intra-Abdominal Fat - blood supply, Intra-Abdominal Fat - drug effects, Intra-Abdominal Fat - metabolism, Intra-Abdominal Fat - pathology, Male, Microscopy, Video, Nitric oxide, Nitric Oxide Synthase Type III - antagonists & inhibitors, Nitric Oxide Synthase Type III - chemistry, Nitric Oxide Synthase Type III - genetics, Nitric Oxide Synthase Type III - metabolism, Obesity, Obesity - drug therapy, Obesity - metabolism, Obesity - pathology, Obesity - physiopathology, Phosphorylation - drug effects, Protein Processing, Post-Translational - drug effects, Rodents, Studies, Subcutaneous Fat, Abdominal - blood supply, Subcutaneous Fat, Abdominal - drug effects, Subcutaneous Fat, Abdominal - metabolism, Subcutaneous Fat, Abdominal - pathology, Tissue Culture Techniques, Vasoconstriction - drug effects, Vasomotor System - drug effects, Vasomotor System - metabolism, Vasomotor System - pathology, Vasomotor System - physiopathology