Batlle D, Redon J, Gutterman C, LaPointe M, Saleh A, Sharma A, Rombola G, Ye M, Alsheikha W, Gomez L
Division of Nephrology and Hypertension, Northwestern University Medical School, Chicago, IL 60611.
J Am Soc Nephrol. 1994 Nov;5(5 Suppl 1):S12-22. doi: 10.1681/ASN.V55s12.
This article reviews work from this laboratory dealing with acid-base status and intracellular pH (pHi) regulation in rat genetic models of hypertension. With freshly isolated thymic lymphocytes, pHi and its regulation were examined in the spontaneously hypertensive rat (SHR). In this rat model, pHi was found to be reduced as compared with that of lymphocytes from normotensive Wistar-Kyoto (WKY) rats. The activity of the Na+/H+ antiporter assessed after stimulation by acute cell acidification was similar in lymphocytes from SHR and WKY rats both in the nominal absence of HCO3- and in media containing HCO3- (22 mM). The kinetic properties of the Na+/H+ antiporter, examined as a function of pHi with the Hill kinetic model, revealed no significant differences between lymphocytes from SHR and WKY rats. The kinetic properties of the Na(+)-dependent and Na(+)-independent Cl(-)-HCO3- exchangers, examined as a function of external Cl-, were also virtually identical in lymphocytes from SHR and WKY rats. Unlike the Na(+)-H+ exchanger and the Na(+)-independent Cl(-)-HCO3- exchanger, which had their highest activities at extremes of pHi (low pHi, Na(+)-H+ exchanger; high pHi, Na(+)-independent Cl(-)-HCO3- exchanger), the Na(+)-dependent Cl(-)-HCO3- exchanger had its maximal activity near steady-state pHi. In Dahl/Rapp salt-sensitive rats with hypertension, the pHi of thymic lymphocytes was also reduced as compared with that of normotensive salt-resistant animals. In this model, renal net acid excretion in salt-sensitive rats was augmented as compared with that of salt-resistant rats. The increase in renal acid excretion was due to an increase in both ammonium and titratable acid excretion and was observed while animals were placed on high, normal and low salt diets. The findings of intracellular acidosis and enhanced renal acid excretion suggest that cellular acid overproduction is augmented in salt-sensitive hypertension.
本文回顾了本实验室关于大鼠高血压遗传模型中酸碱平衡状态及细胞内pH（pHi）调节的研究工作。利用新鲜分离的胸腺淋巴细胞，对自发性高血压大鼠（SHR）的pHi及其调节进行了检测。在该大鼠模型中，发现SHR淋巴细胞的pHi低于正常血压的Wistar-Kyoto（WKY）大鼠淋巴细胞的pHi。在名义上不存在HCO3-以及含有HCO3-（22 mM）的培养基中，经急性细胞酸化刺激后评估的Na+/H+反向转运体活性在SHR和WKY大鼠的淋巴细胞中相似。用希尔动力学模型作为pHi的函数来检测Na+/H+反向转运体的动力学特性，结果显示SHR和WKY大鼠淋巴细胞之间无显著差异。作为细胞外Cl-的函数来检测的Na+依赖性和Na+非依赖性Cl--HCO3-交换体的动力学特性，在SHR和WKY大鼠淋巴细胞中也几乎相同。与在pHi极端值时活性最高的Na+-H+交换体和Na+非依赖性Cl--HCO3-交换体（低pHi时，Na+-H+交换体；高pHi时，Na+非依赖性Cl--HCO3-交换体）不同，Na+依赖性Cl--HCO3-交换体在接近稳态pHi时具有最大活性。在患有高血压的Dahl/Rapp盐敏感大鼠中，胸腺淋巴细胞的pHi也低于正常血压的盐抵抗动物。在该模型中，与盐抵抗大鼠相比，盐敏感大鼠的肾净酸排泄增加。肾酸排泄的增加是由于铵和可滴定酸排泄均增加，且在动物摄入高盐、正常盐和低盐饮食时均观察到这一现象。细胞内酸中毒和肾酸排泄增加的结果表明，盐敏感性高血压中细胞酸产生过多的情况加剧。
