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Vascular thromboxane generation restrains arteriolar hypoxic dilation in skeletal muscle of obese zucker rats
Author(s) -
Goodwill Adam G.,
Hollander John M.,
Brock Robert W.,
James Milinda E.,
Frisbee Jefferson C.
Publication year - 2009
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.23.1_supplement.767.9
Subject(s) - medicine , endocrinology , dilator , hypoxia (environmental) , vascular smooth muscle , chemistry , arteriole , skeletal muscle , microcirculation , oxygen , smooth muscle , organic chemistry
We determined if altered vascular PGI 2 or TxA 2 production with reduced PO 2 contributes to impaired hypoxic dilation of skeletal muscle arterioles of obese Zucker rats (OZR) vs. lean Zucker rats (LZR). Mechanical responses were assessed in isolated arterioles following reduced PO 2 under control conditions and with pharmacological interventions inhibiting arachidonic acid metabolism, NO synthase, and alleviating vascular oxidant stress. Hypoxic dilation, endothelium‐dependent in both, was attenuated in OZR; NOS inhibition had no impact on dilation in either strain. COX inhibition attenuated hypoxic dilation in LZR and abolished responses in OZR. Treating arterioles from OZR with PEG‐SOD improved hypoxic dilation; the improvement was entirely COX‐dependent. Vascular PGI 2 production with hypoxia was similar between strains, although TxA 2 production was increased in OZR; a difference that was attenuated by treatment with PEG‐SOD. Both blockade of PGH 2 /TxA 2 receptors and inhibition of TxA 2 synthase increased hypoxic dilation in OZR arterioles. These results suggest that a contributor to impaired hypoxic dilation of arterioles of OZR may be increased TxA 2 production, which opposes the dilator influences of PGI 2 . These results also suggest that elevated vascular oxidant stress may contribute to the increased TxA2 production and may blunt vascular sensitivity to PGI 2 . (NIH R01 DK64668, AHA EIA 0740129N)