© 1995 American Heart Association, Inc.
Articles |
Relaxation of the Carotid Artery to Hypoxia Is Impaired in Watanabe Heritable Hyperlipidemic Rabbits
From the Departments of Internal Medicine (H.T., F.M.F., T.K., D.D.H.) and Pharmacology (F.M.F., D.D.H.), Center on Aging and Cardiovascular Center, University of Iowa College of Medicine, and the Veterans Administration Medical Center, Iowa City.
Correspondence to Donald D. Heistad, MD, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242.
Abstract We tested the hypothesis that relaxation of the carotid artery during hypoxia is mediated by activation of glibenclamide-sensitive potassium channels and that this response is impaired in hyperlipidemic rabbits. In New Zealand White rabbits (plasma cholesterol, 69±12 mg/dL, mean±SEM) and Watanabe heritable hyperlipidemic (WHHL) rabbits (plasma cholesterol, 677±99 mg/dL), tension of the carotid artery was measured in an organ bath under control conditions and during two levels of hypoxia. In normal rabbits, mild hypoxia produced 21±2% relaxation in arteries precontracted with phenylephrine. Removal of endothelium or the nitric oxide synthase inhibitor NG-nitro-L-arginine (10-4 mol/L) almost abolished relaxation in response to mild hypoxia in normal rabbits. Glibenclamide (10-6 mol/L), an inhibitor of ATP-sensitive potassium channels, attenuated relaxation during mild hypoxia by almost 60%. In WHHL rabbits mild hypoxia relaxed the carotid artery by only 9±4% (P<.05 versus normal rabbits). Severe hypoxia produced greater relaxation of the carotid artery in normal than in WHHL rabbits (85±5% versus 52±8%, respectively, P<.05). Glibenclamide but not endothelial denudation or NG-nitro-L-arginine attenuated relaxation during severe hypoxia in normal and WHHL rabbits. Relaxation of the carotid artery to sodium nitroprusside was similar in normal and WHHL rabbits. These findings suggest that relaxation of the carotid artery in response to mild and severe hypoxia is impaired in WHHL rabbits and is mediated, in large part, by activation of glibenclamide-sensitive potassium channels. Relaxation of the carotid artery in response to mild hypoxia is mediated primarily by endothelium-derived relaxing factor in normal rabbits and impairment of response to mild hypoxia in WHHL is probably secondary to endothelial dysfunction.
Key Words: glibenclamide • ATP-sensitive potassium channels • iberiotoxin • endothelium-derived relaxing factor • NG-nitro-L-arginine
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