AT_2受体通过NO途径降低肾脏近曲小管AT_1受体表达

Effect of AT_2 receptor on AT_1 receptor expression in renal proximal tubule cells through the nitric oxide pathway

目的研究AT2受体激动剂CGP42112对肾脏近曲小管上皮细胞(RPT)AT1受体表达的影响及其作用机制。方法以WKY(Wistar-Kyoto)大鼠的RPT细胞株为研究对象,采用免疫印迹法测定AT2受体激动剂CGP42112对AT1受体蛋白表达的影响,RT-PCR检测AT1受体mRNA表达水平的改变,硝酸还原酶法检测一氧化氮(nitric oxide,NO)含量。结果 AT2受体激动剂CGP42112 10-7mol/L作用24 h可以明显抑制WKY大鼠RPT细胞AT1受体的蛋白与mRNA表达水平(P<0.05)。CGP42112对AT1受体表达的抑制作用可被AT2受体特异性拮抗剂PD123319(10-6mol/L)所阻断。与对照组比较,CGP42112刺激RPT细胞30 min后,NO的合成含量明显升高;NO合成酶抑制剂L-NAME(10-4mol/L)可以阻断CGP42112对AT1受体表达的抑制效应。结论 AT2受体能够抑制WKY大鼠RPT细胞AT1受体的表达水平,该作用可能与NO途径有关。

Objective To study the effect of AT2 receptor on AT1 receptor expression in renal proximal tubule（RPT） cells and its mechanism.Methods RPT cells from Wistar-Kyoto（WKY） rats were used in this study.Effect of CGP42112,an agonist of AT2 receptor,on AT1 receptor expression was detected by Western blotting.mRNA expression level of AT1 receptor and nitric oxide（NO） concentration were measured by RT-PCR and nitrate reductase method,respectively.Results CGP42112 used at the concentration of 10-7mol/L for 24 h significantly decreased the protein and mRNA expression levels of AT1 receptor in RPT cells from WKY rats.The inhibitory effect of CGP42112 on AT1 receptor expression could be blocked by the AT2 receptor antagonist PD123319 at the concentration of 10-6mol/L（P0.05）.The level of synthesized NO in RPT cells was significantly higher in study group than in control group 30 min after CGP42112 was used.The NO synthase inhibitor L-NAME at the concentration of 10-4mol/L could block the inhibitory effect of PD123319 on AT1 receptor expression,indicating that the NO pathway is involved in inhibition of AT2 receptor of RPT cells.Conclusion AT2 receptor can inhibit the expression of AT1 receptor in RPT cells of WKY rats,which may be related to the NO pathway.