ACID-BASE STATUS AND INTRACELLULAR PH REGULATION IN LYMPHOCYTES FROM RATS WITH GENETIC-HYPERTENSION

This article reviews work from this laboratory dealing with acid-base status and intracellular pH (pH(i)) regulation in rat genetic models o f hypertension. With freshly isolated thymic lymphocytes, pH(i) and it s regulation were examined in the spontaneously hypertensive rat (SHR) . In this rat model, pH(i) was found to be reduced as compared with th at of lymphocytes from normotensive Wistar-Kyoto (WKY) rats. The activ ity 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). S he kinetic properties of the Na+/H+ antiporter, examined as a function of pH(i) with the Hill kinetic model, revealed no significant differe nces between lymphocytes from SHR and WKY rats. The kinetic properties of the Na+-dependent and Na+-independent Cl--HCO3- exchangers, examin ed as a function of external Cl-, were also virtually identical in lym phocytes 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 pH(i) (low pH(i), Na+-H+ exchanger; high pH(i), Na+-ind ependent Cl--HCO3- exchanger), the Na+-dependent Cl--HCO3- exchanger h ad its maximal activity near steady-state pH(i). In Dahl/Rapp salt-sen sitive rats with hypertension, the pH(i) of thymic lymphocytes was als o reduced as compared with that of normotensive salt-resistant animals . In this model, renal net acid excretion in salt-sensitive rats was a ugmented as compared with that of salt-resistant rats. The increase in renal acid excretion was due to an increase in both ammonium and titr atable acid excretion and was observed while animals were placed on hi gh, normal and low salt diets. The findings of intracellular acidosis and enhanced renal acid excretion suggest that cellular acid overprodu ction is augmented in salt-sensitive hypertension.