Relaxation of the aorta during hypoxia is impaired in chronically hypertensive rats.
Relaxation of the aorta during hypoxia is impaired in chronically hypertensive rats.
复制标题
慢性高血压大鼠在缺氧期间主动脉的松弛受到损害。
DOI：
10.1161/01.hyp.25.4.735
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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：
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作者：
Taguchi,H;Faraci,FM;Kitazono,T;Heistad,DD
我们研究了缺氧导致主动脉松弛的机制，并检验了这些机制在慢性高血压期间发生改变的假设。在对照条件下和两个缺氧水平下的器官浴中测量血压正常的 Wistar-Kyoto (WKY) 大鼠和易发生中风的自发性高血压大鼠 (SHRSP) 的胸主动脉张力。在 WKY 大鼠中，轻度和重度缺氧导致主动脉（用去氧肾上腺素预收缩）分别松弛 33±4% 和 82±3%（平均值±SEM）。去除内皮或给予一氧化氮合酶抑制剂NG-硝基-L-精氨酸（10−4mol/L）可以消除轻度缺氧时主动脉的松弛，但不影响严重缺氧时的松弛。钾通道抑制剂格列本脲 (10−6mol/L) 在轻度和重度缺氧期间分别减弱主动脉松弛 49±16% 和 74±4%。在SHRSP中，轻度缺氧几乎没有产生主动脉舒张（与WKY相比为3±4%，P<.05）。吲哚美辛不会增加 SHRSP 中轻度缺氧的松弛程度，这表明环氧合酶衍生的收缩因子不会导致松弛受损。在 SHRSP 中，严重缺氧使主动脉松弛 86±4%，而格列本脲则抑制这种反应 60±9%。这些发现表明，WKY 大鼠对轻度缺氧的主动脉舒张主要是由内皮源性舒张因子介导的，而 SHRSP 对轻度缺氧的反应明显受损。相反，严重缺氧期间的松弛在很大程度上是通过格列本脲敏感钾通道的激活介导的，并且在 SHRSP 中保留了对严重缺氧的反应。
We investigated mechanisms by which hypoxia produces relaxation of the aorta and tested the hypothesis that these mechanisms are altered during chronic hypertension. Tension of thoracic aortae from normotensive Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) was measured in an organ bath under control conditions and at two levels of hypoxia. In WKY rats, mild and severe hypoxia produced relaxation of the aortae (precontracted with phenylephrine) by 33±4% and 82±3%, respectively (mean±SEM). Removal of endothelium or administration ofNG-nitro-l-arginine (10−4mol/L), an inhibitor of nitric oxide synthase, abolished relaxation of the aortae in response to mild hypoxia but did not affect relaxation during severe hypoxia. Glibenclamide (10−6mol/L), an inhibitor of potassium channels, attenuated relaxation of the aortae during mild and severe hypoxia by 49±16% and 74±4%, respectively. In SHRSP, mild hypoxia produced little relaxation of the aortae (3±4%,P<.05 compared with WKY). Indomethacin did not increase relaxation to mild hypoxia in SHRSP, which suggests that a cyclooxygenase-derived contracting factor does not contribute to impaired relaxation. Severe hypoxia relaxed the aortae by 86±4% in SHRSP, and glibenclamide inhibited this response by 60±9%. These findings suggest that relaxation of the aorta in response to mild hypoxia in WKY rats is mediated primarily by endothelium-derived relaxing factor, and the response to mild hypoxia is markedly impaired in SHRSP. In contrast, relaxation during severe hypoxia is mediated, in large part, by activation of glibenclamide-sensitive potassium channels, and the response to severe hypoxia is preserved in SHRSP.