高血压发生中多巴胺D4受体对肾脏近曲小管细胞血管紧张素Ⅱ1型受体的异常调控  

Down-regulation of D_4 Dopamine Receptor on Angiotensin Ⅱ Type 1 Receptor Expression in Rat Renal Proximal Tubule Cells

作　　者：邓昆[1] 黄河飞[1] 石伟彬[1] 何多芬[1] 杨成明[1] 王旭开[1] 黄岚[2] 曾春雨[1] 

机构地区：[1]第三军医大学大坪医院(野战外科研究所)心内科心血管病研究室,重庆400042 [2]第三军医大学新桥医院心内科,重庆400037

出　　处：《中华高血压杂志》2008年第8期724-727,共4页Chinese Journal of Hypertension

基　　金：国家自然基金资助项目(30470728、30672199);国家科技部973前期研究专项(2008CB5173008)

摘　　要：目的研究多巴胺 D_4受体对肾脏近曲小管上皮(RPT)细胞上血管紧张素Ⅱ1型受体(AT_1R)表达的异常调控在原发性高血压(EH)发生中的作用。方法以 Wistar-Kyoto(WKY)大鼠的 RPT 细胞株作为研究对象,采用免疫印迹法测定刺激 D_4受体后 AT_1R 的表达变化,并观察其作用机制及信号途径。结果 D_4受体激动剂PD168077(10^(-6)mol/L,24 h)刺激 D_4受体可明显抑制 WKY 大鼠 RPT 细胞 AT_1R 的表达,该作用呈现浓度和时间依赖性关系;PD168077对 AT_1R 表达的抑制作用可被 D_4受体特异性阻断剂 L745870(10^(-6)mol/L)所阻断;相反,在 EH 状态下这种作用受损,PD168077反而增加 AT_1R 的表达。在钙通道拮抗剂尼卡地平存在的情况下 D_4受体对 WKY 细胞 AT_1R 的抑制作用被阻断,提示 D_4受体对 AT_1R 的下调作用可能通过钙通道途径发生影响。结论D_4受体对 AT_1R 蛋白表达具有抑制作用,该作用受损可能在高血压的发生、发展过程中发挥一定作用。Objective To investigate the aberrant regulation of D4 dopamine receptor on angiotensin Ⅱ type 1 receptor（AT1R） in renal proximal tubule cells from spontaneously hypertensive rats （SHR）. Methods The renal proximal tubule cells from Wistar-Kyoto（WKY） rats and SHRs were used in this study, the effect of D4 receptor on AT1R protein expression was determined by immunoblotting. Results A D4 agonist PD168077 decreased AT1R expression in a concentration- and time-dependent manner; these effects were blocked by the D4 antagonist L745870. However, in SI-IR cells, the inhibitory effect of D4 receptor on AT1R was lost, activation of D4 receptor increased AT1 R protein expression. The D4 agonlst PD168077 increases the expression of AT1 Rs. In the presence of calcium channel blocker, nicardipine, the inhibitory effect of D4 receptor on AT1 R was blocked in WKY cells, indicating that the calcium entry is involved into the signal pathway. Conclusion The aberrant inhibitory effect of D4 receptor on AT1 R expression might be involved into the pathogenesis of essential hypertension.

关 键 词：D4多巴胺受体 血管紧张素Ⅱ1型受体 肾脏近曲小管上皮细胞 原发性高血压 

分 类 号：R544.1[医药卫生—心血管疾病] R749.302[医药卫生—内科学]