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G蛋白偶联受体激酶4对内皮素B型受体的异常调节在原发性高血压发生中的作用

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Keywords: 内皮素B型受体,G蛋白偶联受体激酶,尿钠排泄,原发性高血压

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Abstract:

目的探讨G蛋白偶联受体激酶4(Gprotein-coupledreceptorkinase4,GRK4)对内皮素B型受体(endothelinreceptorB,ETB)的异常调节在原发性高血压中的作用及机制。方法选用12~14周龄,体质量300g左右的雄性自发性高血压大鼠(spontaneouslyhypertensiverats,SHRs)及其对照鼠(Wistar-Kyoto,WKY)各10只,通过无创鼠尾测压仪测定血压,采用右肾上腺静脉插管灌注ETB受体特异性激动剂BQ3020后观察尿流速及尿钠排泄率,荧光定量PCR检测大鼠肾脏GRK4mRNA水平,Westernblot测定大鼠肾脏GRK4及ETB受体的蛋白表达差异,免疫共沉淀法检测ETB受体磷酸化情况,在动物水平观察高血压状态下ETB受体的功能情况。结果ETB受体激动剂BQ3020对WKY大鼠有明显利尿排钠作用,且这种利尿排钠作用可以被ETB受体抑制剂BQ788阻断,但在SHR大鼠BQ3020的利尿排钠作用受损[尿流速:(11.23±2.16)vs(3.49±1.32),P<0.05];尿钠排泄率:[(1551.43±393.47)vs(601.16±128.15),P<0.05];在SHR大鼠肾皮质GRK4的蛋白水平及mRNA水平均较WKY大鼠高[蛋白:(1.38±0.10)vs(0.85±0.07),P<0.05];mRNA:[(2.23±0.15)vs(0.78±0.16),P<0.05],SHR大鼠ETB受体总蛋白水平与WKY大鼠相比差异无统计学意义(P>0.05),但ETB受体磷酸化水平增高。结论GRK4可能通过对内皮素B型受体的异常调节,参与了原发性高血压发生与发病。

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