Effect of renal injury-induced neurogenic hypertension on NO synthase, caveolin-1, AKt, calmodulin and soluble guanylate cyclase expressions in the kidney.
Effect of renal injury-induced neurogenic hypertension on NO synthase, caveolin-1, AKt, calmodulin and soluble guanylate cyclase expressions in the kidney.
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肾损伤引起的神经源性高血压对肾脏中NO合酶、caveolin-1、AKt、钙调蛋白和可溶性鸟苷酸环化酶表达的影响。
DOI：
10.1152/ajprenal.00157.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Vaziri,ND
中科院分区：
文献类型：
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作者：
Bai,Y;Ye,S;Mortazavi,R;Campese,V;Vaziri,ND
将少量苯酚单次注射到大鼠的一个肾脏皮质中导致持续性高血压（HTN）的发展，其被认为是由肾传入和传出交感神经通路的激活和钠潴留介导的。一氧化氮（NO）在调节肾血管阻力、肾小管Na+重吸收、压力性尿钠排泄以及由此调节全身动脉压中起主要作用。本研究旨在验证慢性肾损伤引起的HTN可能与肾脏NO系统失调有关的假设。因此，尿NO代谢物（NOx）和cGMP排泄以及肾皮质组织（右肾）表达NO合酶（NOS）亚型[分别为内皮型、神经型和诱导型NOS（eNOS、nNOS和iNOS）]、NOS调节因子（小窝蛋白-1、磷酸-AKt和钙调蛋白），第二信使系统在注射苯酚后4周，测定雄性Sprague-Dawley大鼠的可溶性鸟苷酸环化酶[sGC]和磷酸二酯酶-5 [PDE-5（50 μl 10%苯酚）或生理盐水注入左肾下极。酚注射组动脉压显著升高，尿NO_x和cGMP排泄显著减少，肾组织nNOS、eNOS、Phospho-eNOS、iNOS和sGC α链表达下调。然而，肾组织AKt，磷酸化AKT，钙调蛋白，PDE-5蛋白质在苯酚注射的动物中没有变化。总之，该模型中的肾损伤导致NOS同工型和sGC的显著下调以及随后的肾脏NO产生和cGMP产生的减少，这些事件可能有助于该模型中HTN的维持。
Single injection of a small quantity of phenol into the cortex of one kidney in rats results in development of persistent hypertension (HTN) which is thought to be mediated by activation of renal afferent and efferent sympathetic pathways and sodium retention. Nitric oxide (NO) plays a major role in regulation of renal vascular resistance, tubular Na+reabsorption, pressure natriuresis, and thereby systemic arterial pressure. The present study was performed to test the hypothesis that chronic renal injury-induced HTN may be associated with dysregulation of NO system in the kidney. Accordingly, urinary NO metabolite (NOx) and cGMP excretions as well as renal cortical tissue (right kidney) expressions of NO synthase (NOS) isoforms [endothelial, neuronal, and inducible NOS, respectively (eNOS, nNOS, and iNOS)], NOS-regulatory factors (Caveolin-1, phospho-AKt, and calmodulin), and second-messenger system (soluble guanylate cyclase [sGC] and phosphodiesterase-5 [PDE-5]) were determined in male Sprague-Dawley rats 4 wk after injection of phenol (50 μl of 10% phenol) or saline into the lower pole of left kidney. The phenol-injected group exhibited a significant elevation of arterial pressure, marked reductions of urinary NOxand cGMP excretions, downregulations of renal tissue nNOS, eNOS, Phospho-eNOS, iNOS, and alpha chain of sGC. However, renal tissue AKt, phospho-AKT, Calmodulin, and PDE-5 proteins were unchanged in the phenol-injected animals. In conclusion, renal injury in this model results in significant downregulations of NOS isoforms and sGC and consequent reductions of NO production and cGMP generation by the kidney, events that may contribute to maintenance of HTN in this model.