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K ATP ‐mediated vasodilation is impaired in obese Zucker rats
Author(s) -
Hodnett Benjamin Lucas,
Xiang Lusha,
Hester Robert L.
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.a480-a
Subject(s) - cromakalim , vasodilation , glibenclamide , agonist , medicine , endocrinology , chemistry , potassium channel , iloprost , pharmacology , receptor , prostacyclin , diabetes mellitus
Vascular reactivity and functional vasodilation are attenuated in the obese Zucker rat (OZ), an animal model of the metabolic syndrome. PGI 2 , an endothelial mediator of functional vasodilation, causes vasodilation through IP receptor signaling and activation of ATP‐sensitive K + channels (K ATP ). The OZ exhibits an attenuated vasodilation to iloprost, a PGI 2 ‐analog, and IP receptor agonist. We hypothesize that the impaired IP‐induced vasodilation in the OZ is due to altered K ATP responses. In this study we determined if K ATP ‐mediated vasodilation was impaired in the OZ. Small gracilis arteries from 10 – 12 week old lean (LZ) and OZ were isolated, cannulated, and pressurized to 80 mmHg (n = 5 for each group). Changes in luminal diameter were determined in response to increasing cumulative concentrations of the K ATP ‐channel opener, cromakalim (0.01 – 10 μM), both in the absence and presence of the K ATP ‐channel inhibitor, glibenclamide (10 μM). Baseline diameters were not different between LZ (177 ± 7 μm) and OZ (175 ± 11 μm). The vasodilatory responses to cromakalim concentrations of 0.1 – 1.0 μM were significantly attenuated in the OZ as compared to the LZ. Glibenclamide completely inhibited the vasodilatory responses to all concentrations of cromakalim. The right shift in the concentration response curve suggests a decrease in the sensitivity of K ATP channels in vascular smooth muscle of the OZ. Supported by HL‐51971.