Intact microtubules are required for natriuretic responses to nitric oxide and increased renal perfusion pressure.
Intact microtubules are required for natriuretic responses to nitric oxide and increased renal perfusion pressure.
复制标题
对一氧化氮的利尿钠反应和增加的肾灌注压需要完整的微管。
DOI：
10.1161/hypertensionaha.107.103036
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Carey,RobertM
中科院分区：
文献类型：
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作者：
Park,Jennifer;Kemp,BrandonA;Howell,NancyL;Gildea,JohnJ;Keller,SusannaR;Carey,RobertM
细胞外肾间质（RI）cGMP调节NO和压力诱导的尿钠排泄在体内大鼠。本研究的目的是测试的假设，一个完整的微管蛋白网络是必需的cGMP从细胞内的网站到细胞外室在体内的运输，这种运输所需的一氧化氮和增加肾灌注压诱导的钠尿。在1小时的对照期后，单侧肾切除大鼠接受NO供体S-亚硝基-N-乙酰青霉胺（SNAP），SNAP+微管抑制剂诺考达唑（NOC），SNAP+NOC+cGMP或NOC单独RI输注，连续2个1小时的收集期。SNAP单独使用可增加RI、cGMP（P<0.05）和尿钠排泄量（1小时P<0.05，2小时P <0.005）。相反，当SNAP+NOC联合输注时，RI cGMP或尿钠排泄均未增加。然而，当cGMP与SNAP+NOC联合输注时，对SNAP的利钠反应完全恢复。同样，NOC取消SNAP诱导的Na+和Li+排泄分数的增加。NOC也防止增加RI cGMP和尿钠排泄引起的提高肾灌注压在uninephrectomized大鼠，和压力尿钠排泄重新建立的共同管理RI cGMP。如在体内肾灌注固定后的共聚焦显微镜所示，在肾内注入NOC的肾皮质肾单位中β-微管蛋白被破坏。这些观察结果表明，需要一个功能微管蛋白网络的cGMP运输到细胞外空间，以调节NO和压力诱导的尿钠排泄。
Extracellular renal interstitial (RI) cGMP modulates NO- and pressure-induced natriuresis in vivo in the rat. The present study objective was to test the hypothesis that an intact microtubulin network is required for transport of cGMP from intracellular sites into the extracellular compartment in vivo and that this transport is required for natriuresis induced by NO and increased renal perfusion pressure. After a 1-hour control period, uninephrectomized rats received an RI infusion of NO donorS-nitroso-N-acetylpenicillamine (SNAP), SNAP+microtubule inhibitor nocodazole (NOC), SNAP+NOC+cGMP, or NOC alone for 2 consecutive 1-hour collection periods. SNAP alone increased RI cGMP (P<0.05 during both experimental periods) and urinary sodium excretion (P<0.05 at 1 hour andP<0.005 at 2 hours). In contrast, when SNAP+NOC were coinfused, there was no increase in either RI cGMP or urinary sodium excretion. However, when cGMP was coinfused with SNAP+NOC, the natriuretic response to SNAP was fully restored. Similarly, NOC abolished SNAP-induced increases in the fractional excretion of Na+and Li+. NOC also prevented the increase in both RI cGMP and natriuresis engendered by raising renal perfusion pressure in uninephrectomized rats, and pressure-natriuresis was re-established by coadministration of RI cGMP. As demonstrated by confocal microscopy after in vivo renal perfusion fixation, β-tubulin was disrupted in renal cortical nephrons of kidneys infused intrarenally with NOC. These observations indicate that a functioning microtubulin network is required for the transport of cGMP into the extracellular space to modulate NO- and pressure-induced natriuresis.