Taguchi H, Faraci F M, Kitazono T, Heistad D D
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Arterioscler Thromb Vasc Biol. 1995 Oct;15(10):1641-5. doi: 10.1161/01.atv.15.10.1641.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
缺氧时颈动脉的舒张是由格列本脲敏感钾通道的激活介导的，并且高脂血症兔的这种反应受损。在新西兰白兔（血浆胆固醇，69±12mg/dL，平均值±标准误）和渡边遗传性高脂血症（WHHL）兔（血浆胆固醇，677±99mg/dL）中，在对照条件下以及两种缺氧水平期间，在器官浴中测量颈动脉张力。在正常兔中，轻度缺氧使预先用去氧肾上腺素收缩的动脉产生21±2%的舒张。去除内皮或一氧化氮合酶抑制剂NG-硝基-L-精氨酸（10⁻⁴mol/L）几乎消除了正常兔对轻度缺氧的舒张反应。格列本脲（10⁻⁶mol/L），一种ATP敏感性钾通道抑制剂，使轻度缺氧期间的舒张减弱了近60%。在WHHL兔中，轻度缺氧仅使颈动脉舒张9±4%（与正常兔相比，P<.05）。重度缺氧使正常兔的颈动脉舒张程度大于WHHL兔（分别为85±5%和52±8%，P<.05）。格列本脲而非内皮剥脱或NG-硝基-L-精氨酸减弱了正常兔和WHHL兔重度缺氧期间的舒张。正常兔和WHHL兔对硝普钠的颈动脉舒张反应相似。这些发现表明，WHHL兔对轻度和重度缺氧的颈动脉舒张反应受损，并且在很大程度上是由格列本脲敏感钾通道的激活介导的。（摘要截断于250字）
