Relaxation of the carotid artery to hypoxia is impaired in Watanabe heritable hyperlipidemic rabbits.
Relaxation of the carotid artery to hypoxia is impaired in Watanabe heritable hyperlipidemic rabbits.
复制标题
渡边遗传性高脂血症兔颈动脉对缺氧的舒张受到损害。
DOI：
10.1161/01.atv.15.10.1641
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Heistad,DD
中科院分区：
文献类型：
--
作者：
Taguchi,H;Faraci,FM;Kitazono,T;Heistad,DD
我们检验了这一假设，即在缺氧过程中颈动脉的舒张是由格列本脲敏感性钾通道的激活介导的，并且这种反应在高血压兔中受损。在新西兰白色兔（血浆胆固醇，69±12 mg/dL，平均值±SEM）和Watanabe遗传性高脂血症（WHHL）兔（血浆胆固醇，677±99 mg/dL）中，在对照条件下和两种缺氧水平下的器官浴中测量颈动脉张力。在正常家兔中，轻度缺氧可使苯肾上腺素预收缩的动脉舒张21±2%。去除内皮细胞或一氧化氮合酶抑制剂NG-硝基-L-精氨酸（10− 4 mol/L）几乎可以消除正常家兔对轻度缺氧的舒张反应。格列本脲（10− 6 mol/L）是ATP敏感性钾通道的抑制剂，在轻度缺氧时可使舒张减弱近60%。在WHHL兔中，轻度缺氧仅使颈动脉松弛9±4%（与正常兔相比P<0.05）。重度缺氧使正常兔颈动脉舒张大于WHHL兔（分别为85±5%和52± 8%，P<0.05）。在正常和WHHL兔中，格列本脲而非内皮剥脱或NG-硝基-L-精氨酸可减弱严重缺氧时的舒张作用。硝普钠对正常兔和WHHL兔颈动脉的舒张作用相似。这些结果表明，在WHHL兔中，颈动脉对轻度和重度缺氧的舒张反应受损，并且在很大程度上是通过激活格列本脲敏感性钾通道介导的。在正常兔中，颈动脉对轻度缺氧的舒张反应主要由内皮源性舒张因子介导，而WHHL对轻度缺氧的反应受损可能继发于内皮功能障碍。
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 inhibitorNG-nitro-l-arginine (10−4mol/L) almost abolished relaxation in response to mild hypoxia in normal rabbits. Glibenclamide (10−6mol/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 orNG-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.