Acid-base status and intracellular pH regulation in lymphocytes from rats with genetic hypertension.

Abstract

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.