Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na+-K+-2Cl- cotransporter

Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na+-K+-2Cl- cotransporter
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DOI:
10.1152/ajpheart.00083.2002
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发表时间:
2002-11-01
影响因子:
4.8
通讯作者:
Shull, GE
Shull, GE
中科院分区:
医学2区
文献类型:
--
作者:
Meyer, JW;Flagella, M;Shull, GE

文献摘要

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基底外侧Na ~+-K ~+-2Cl(-)协同转运蛋白(NKCC 1)在维持细胞电解质和容量稳态中发挥重要作用。NKCC 1缺陷(Nkcc 1(-/-))小鼠用于检查其在心脏功能和维持血压和血管张力中的作用。尾袖测量表明,清醒的Nkcc 1(-/-)小鼠的收缩压显著低于野生型(Nkcc 1(+/+))小鼠(分别为114.5 +/- 2.2和131.8 +/- 2.5 mmHg)。血清醛固酮水平正常,表明细胞外液量稳态未受损。在股动脉和左心室中使用压力传感器的研究表明,麻醉的Nkcc 1(-/-)小鼠的平均动脉压和左心室压降低,而心肌收缩参数与Nkcc 1(+/+)小鼠的心肌收缩参数没有显著差异。当用苯肾上腺素刺激时,来自Nkcc 1(+/+)和Nkcc 1(-/-)小鼠的主动脉平滑肌在最大收缩力方面没有表现出显著差异,并且仅表现出中等剂量反应变化。然而,在来自Nkcc 1(-/-)小鼠的阶段性门静脉平滑肌中,注意到机械力急剧降低。这些结果表明,NKCC 1对于维持正常血压和血管张力可能是重要的。
The basolateral Na+-K+-2Cl(-) cotransporter (NKCC1) functions in the maintenance of cellular electrolyte and volume homeostasis. NKCC1-deficient (Nkcc1(-/-)) mice were used to examine its role in cardiac function and in the maintenance of blood pressure and vascular tone. Tail-cuff measurements demonstrated that awake Nkcc1(-/-) mice had significantly lower systolic blood pressure than wild-type (Nkcc1(+/+)) mice (114.5 +/- 2.2 and 131.8 +/- 2.5 mmHg, respectively). Serum aldosterone levels were normal, indicating that extracellular fluid-volume homeostasis was not impaired. Studies using pressure transducers in the femoral artery and left ventricle showed that anesthetized Nkcc1(-/-) mice have decreased mean arterial pressure and left ventricular pressure, whereas myocardial contraction parameters were not significantly different from those of Nkcc1(+/+) mice. When stimulated with phenylephrine, aortic smooth muscle from Nkcc1(+/+) and Nkcc1(-/-) mice exhibited no significant differences in maximum contractility and only moderate dose-response shifts. In phasic portal vein smooth muscle from Nkcc1(-/-) mice, however, a sharp reduction in mechanical force was noted. These results indicate that NKCC1 can be important for the maintenance of normal blood pressure and vascular tone.