自发性高血压大鼠发育过程中D_1多巴胺受体对钠-氢交换体3的调节  

Regulation of NHE3 by D_1 dopamine receptor during development of spontaneously hypertensive rats

作　　者：李晓曦[1] Frederick E Albrecht 徐镜 Jean E Robillard Gilbert M Eisner Pedro A Jose 

机构地区：[1]中山医科大学附属第一医院外科,广州510080 [2]Georgetown [3]University [4]Georgetown University Medical Center

出　　处：《中华医学杂志》2001年第9期549-552,共4页National Medical Journal of China

基　　金：美国国立卫生研究所研究基金资助项目 (DK3 93 0 8;DK447 56;HL2 3 0 81;HL5853 6 )

摘　　要：目的　探讨是否原发性高血压继发于多巴胺受体、G蛋白和Na+ H+ 交换体 3(NHE3)的相互作用障碍。方法　为避免第二信使的影响 ,我们采用无细胞质成分的肾小管细胞膜刷状缘进行实验 ,实验对象为高血压产生前 (2～ 3周龄 )和高血压产生后 (12周龄 )的自发性高血压大鼠 (SHR) ,研究多巴胺受体激活剂对SHR肾小管细胞膜刷状缘的NHE活性的抑制作用和对G蛋白亚基与NHE3结合的影响。结果　正常对照鼠 (WKY鼠 )NHE3活性随年龄增长而增强 ,但SHR肾NHE3活性未随年龄变化而改变。SHR与WKY鼠的D1多巴胺受体表达不受年龄影响。多巴胺D1受体激活剂对WKY肾NHE3活性的抑制能力随年龄增长而增强 ,但对SHR的抑制未随年龄变化。多巴胺D1受体激活剂 (Fenoldopam)增加WKY幼鼠Gsα/NHE3结合量与成年鼠相同 ,但使SHR幼鼠Gsα/NHE3结合量减少。结论　多巴胺D1受体激活剂对SHR中NHE3活性的抑制减少早于高血压的形成 。Objective To determine if spontaneous hypertension is secondary to defective interaction among dopamine receptor, G protein, and Na +/H + exchanger 3 (NHE3). Methods The inhibitory effect of a D 1 dopamine agonist upon NHE3 activity and its impact upon Gsα/NHE3 binding in renal brush border membrane (BBM) of spontaneously hypertensive rats (SHRs) 2～3 weeks before and 12 weeks after the establishment of hypertension were examined. In order to avoid the confounding influence of second messenger on D 1 receptor/NHE3 interaction, study was made in BBM devoid of cytoplasmic component. Results NHE3 activity increased with age in Wister Kyoto (WKY) rats but not in SHRS. D1 receptor expression did change with age in both WKY rats and SHRs. The inhibitory effect of a D 1 like agonist on NHE3 activity increased with age in WKY rats but not in SHRs. In WKY rats, another D 1 like agonist, fedoldopam, increased Gsα/NHE3 binding to the same extent in 2 week old and adult rats, but decreased the amount of Gsαbound to NHE3 in 2 week old SHRs. Conclusion The decrease of inhibitory effect of D 1 like agonist upon NHE3 activity in SHRs precedes the development of hypertension. Spontaneous hypertension may be caused, in part, by a decreased interaction between Gsα and NHE3 in BBM secondary to D 1 like receptor function.

关 键 词：自发性高血压 多巴胺受体 钠-氢交换体3 蛋白质G 

分 类 号：R544.1[医药卫生—心血管疾病]