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Up‐regulated COX‐2 and impaired functional vasodilation in obese Zucker rats
Author(s) -
Xiang Lusha,
Abram Sean
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a494-b
Subject(s) - vasodilation , endocrinology , medicine , cyclooxygenase , vasoconstriction , thromboxane , antagonist , arachidonic acid , thromboxane a2 , stimulation , chemistry , receptor , enzyme , biochemistry , platelet
Exercise is a treatment option for obesity. However, in obesity there is an attenuated increase in muscle blood flow, functional dilation (FD) in response to exercise. Arachidonic acid (AA) metabolism is important in mediating functional vasodilation (FD). Obese Zucker rats (OZ) exhibit impaired FD due to an altered AA metabolism, resulting in an increased thromboxane receptor (TP) mediated vasoconstriction. We hypothesize that the impaired FD is due to up‐regulation of COX‐2. Lean (LZ) and OZ (11–12 wk) were treated with the selective cyclooxygenase‐2 (COX‐2) inhibitor Celebrex (10 mg/kg) by daily oral gavage for 1–2 weeks. The animals were anesthetized and the spinotrapezius muscle was prepared for microcirculatory studies. Arcade arteriolar diameter was measured following muscle stimulation in the absence and presence of the TP antagonist SQ 29548 (SQ). OZ exhibited significantly higher plasma IL‐6 levels (854 ± 319 pg/ml) as compared to LZ (171 ± 9 pg/ml). Mean arterial pressures were not significantly different between groups. Functional dilations were impaired in the OZ with Celebrex treatment improving the FD. SQ improved the vasodilatory responses in obese controls with no effect in lean or Celebrex treated groups ( Fig). These results suggest that the impaired FD associated with enhanced TP receptor‐mediated vasoconstriction in OZ is due in part to an inflammatory‐induced upregulation of COX‐2.