Sequential changes in renal expression of renin-angiotensin system genes in acute unilateral ureteral obstruction.
Sequential changes in renal expression of renin-angiotensin system genes in acute unilateral ureteral obstruction.
复制标题
急性单侧输尿管梗阻中肾素-血管紧张素系统基因的肾脏表达的连续变化。
DOI：
10.1038/ki.1995.408
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发表时间：
1995
影响因子：
19.6
通讯作者：
Martínez-Maldonado,M
中科院分区：
文献类型：
--
作者：
PimentelJr,JL;Montero,A;Wang,S;Yosipiv,I;el-Dahr,S;Martínez-Maldonado,M
急性单侧输尿管梗阻患者肾脏肾素-血管紧张素系统基因表达的时序性变化。单侧输尿管梗阻(UUO)改变了肾素-血管紧张素系统(RAS)基因的表达。我们验证了RAS基因表达在梗阻后不久发生变化的假设。事实上，在UUO的前24小时内的测量结果显示，梗阻的肾脏在1小时内肾素mRNA表达上调。UUO还导致肾小球肾素含量、肾素含量、血管紧张素转换酶活性和血管紧张素转换酶II浓度升高。梗阻后1、2、6、24小时肾组织肾素mRNA相对丰度较基础值升高，对侧肾组织肾素基因表达降低。与对侧和假手术组相比，梗阻组大鼠肾脏在6小时和24小时时AT1-R基因表达减弱。血管紧张素转换酶活性在梗阻侧肾中上调，在对侧肾中短暂下调。这些结果首次表明，RAS的激活是UUO后1小时的结果，肾素mRNA的上调和ACE活性的上调导致Ang II的产生增加，而Ang II的合成早在UUO后6小时就下调了AT1-R的表达。这些研究建立了急性UUO中RAS基因的顺序、差异调节模式，为这种情况下的血流动力学变化提供了解释。
Sequential changes in renal expression of renin-angiotensin system genes in acute unilateral ureteral obstruction. Unilateral ureteral obstruction (UUO) alters the expression of genes encoding for the renin-angiotensin system (RAS). We tested the hypothesis that changes in RAS genes expression occur soon after obstruction. Indeed, measurements during the first 24 hours of UUO showed up-regulation of renin mRNA in the obstructed kidney at 1 hour. UUO also led to increases in PRA and renal renin content, ACE activity and Ang II concentration in the experimental kidney. The obstructed kidney relative abundance of renin mRNA was increased compared to basal at 1, 2, 6, and 24 hours; the contralateral kidney renin mRNA expression was reduced. AT1-R mRNA expression was diminished at 6 and 24 hours in the obstructed kidney compared to contralateral and sham kidneys. ACE activity was up-regulated in the obstructed kidney and transiently down-regulated in the contralateral kidney. These findings show for the first time that activation of the RAS results from as little as 1 hour of UUO and that up-regulation of renin mRNA and ACE activity lead to increase Ang II production which down-regulates AT1-R mRNA as early as 6 hours post-UUO. These studies establish a pattern of sequential, differential regulation of the RAS genes in acute UUO that provide an explanation for the hemodymamic changes in this condition.