Effect of the Na-K-2Cl cotransporter NKCC1 on systemic blood pressure and smooth muscle tone.
Effect of the Na-K-2Cl cotransporter NKCC1 on systemic blood pressure and smooth muscle tone.
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DOI：
10.1152/ajpheart.01402.2006
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发表时间：
2007-05
期刊：
影响因子：
--
通讯作者：
O'Neill WC
中科院分区：
文献类型：
--
作者：
Garg P;Martin CF;Elms SC;Gordon FJ;Wall SM;Garland CJ;Sutliff RL;O'Neill WC
在大鼠主动脉中的研究表明，Na-K-2Cl协同转运蛋白NKCC 1被血管收缩剂激活，被硝基血管扩张剂抑制，有助于体外平滑肌张力，并在高血压中上调。为了确定NKCC 1在全身血管阻力和高血压中的作用，在用布美他尼抑制NKCC 1之前和之后测量大鼠的血压。静脉输注足以产生高于NKCC 1的IC 50的游离血浆浓度的布美他尼，使血压立即下降5.2%（P < 0.001）。当夹闭肾动脉时，未阻止降低，表明这不是由于布美他尼的肾脏作用。布美他尼没有改变NKCC 1基因敲除小鼠的血压，表明它是通过NKCC 1特异性发挥作用的。在三级肠系膜动脉中，布美他尼可释放的86 Rb流出量被苯乙哌啶急性刺激133%，布美他尼降低了对苯乙哌啶的收缩反应，表明NKCC 1影响阻力血管的张力。布美他尼的降压作用在通过7天去甲肾上腺素输注造成高血压的大鼠中成比例地更大（12.7%，p < 0.001，与血压正常的大鼠相比），但当通过固定的主动脉缩窄造成高血压时（8.0%），布美他尼的降压作用要小得多，这再次与布美他尼对阻力血管的作用而不是对血压的其他决定因素的作用一致。我们的结论是，NKCC 1通过影响阻力血管中的平滑肌张力来影响血压，并且这种影响在高血压中增强。
Studies in rat aorta have shown that the Na-K-2Cl cotransporter NKCC1 is activated by vasoconstrictors and inhibited by nitrovasodilators, contributes to smooth muscle tone in vitro, and is upregulated in hypertension. To determine the role of NKCC1 in systemic vascular resistance and hypertension, blood pressure was measured in rats before and after inhibition of NKCC1 with bumetanide. Intravenous infusion of bumetanide sufficient to yield a free plasma concentration above the IC50 for NKCC1 produced an immediate drop in blood pressure of 5.2 % (P < 0.001). The reduction was not prevented when the renal arteries were clamped, indicating that it was not due to a renal effect of bumetanide. Bumetanide did not alter blood pressure in NKCC1 null mice, demonstrating that it was acting specifically through NKCC1. In third-order mesenteric arteries, bumetanide-inhibitable efflux of 86Rb was acutely stimulated 133 % by phenylephrine, and bumetanide reduced the contractile response to phenylephrine, indicating that NKCC1 influences tone in resistance vessels. The hypotensive effect of bumetanide was proportionately greater in rats made hypertensive by a 7-day infusion of norepinephrine (12.7 %, p < 0.001 vs. normotensive rats) but much less so when hypertension was produced by a fixed aortic coarctation (8.0 %), again consistent with an effect of bumetanide on resistance vessels rather than other determinants of blood pressure. We conclude that NKCC1 influences blood pressure through effects on smooth muscle tone in resistance vessels and that this effect is augmented in hypertension.
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影响因子：
8.3
作者：
Jiang, GR;Cobbs, S;O'Neill, WC
通讯作者：
O'Neill, WC
DOI：
10.1152/ajpheart.1998.275.1.h151
发表时间：
1998-07-01
影响因子：
4.8
作者：
Lamb, FS;Barna, TJ
通讯作者：
Barna, TJ
DOI：
10.1152/ajpheart.01192.2003
发表时间：
2004-10-01
影响因子：
4.8
作者：
Janssen, BJA;De Celle, T;Smith, TL
通讯作者：
Smith, TL
DOI：
10.1152/ajpheart.00083.2002
发表时间：
2002-11-01
影响因子：
4.8
作者：
Meyer, JW;Flagella, M;Shull, GE
通讯作者：
Shull, GE
影响因子：
--
作者：
GARWITZ, ET;JONES, AW
通讯作者：
JONES, AW