Renal apical membrane sodium-hydrogen exchange in genetic salt-sensitive hypertension

Academic Article

Abstract

  • Inbred Dahl/Rapp salt-sensitive and salt-resistant rats differ in their blood pressure response to dietary salt. We studied sodium-hydrogen (Na-H) exchanger kinetics in renal brush border membrane vesicles prepared from both strains on either a 1% or 8% NaCl diet. Kinetics measurements were made with the acridine orange fluorescence quenching technique in vesicles prepared at pH 6.0. The initial Na-H exchange rate was measured using preparations with similar initial quench values. The maximal transport rate (V(max), fluorescence units per second per milligram protein [±SEM]) in salt- sensitive rats on a 1% NaCl diet was significantly lower than that in salt- resistant rats (36.9±4.4 versus 51.8±5.5, respectively, P<.0005). With the 8% NaCl diet for 1 week, the V(max) of salt-resistant rats decreased and became similar to that of salt-sensitive rats. The affinity for sodium (K(m), millimoles per liter [±SEM]) was also lower in salt-sensitive rats than in salt-resistant rats while on a 1% NaCl diet (11.8±1.0 versus 19.6±2.3, respectively, P<.002). These values converged when both strains were fed an 8% NaCl diet for 1 week. Inhibition by 25 μmol/L amiloride was less in salt- sensitive rats than in salt-resistant rats on the 1% NaCl diet. These results show that salt-sensitive rats have lower renal apical membrane Na-H exchange activity than salt-resistant rats on a 1% NaCl diet. Salt-sensitive rats do not modulate renal apical membrane Na-H exchange in response to an 8% NaCl diet, whereas salt-resistant rats show a more physiologically appropriate response to increased dietary salt. The maladaptive response by salt- sensitive rats on a high salt diet may well contribute to the development of severe hypertension under these conditions. The differences between these two strains in sodium affinity and amiloride inhibition suggest structural differences in the renal apical membrane Na-H exchangers at the substrate and amiloride binding sites or altered cellular regulation of these transport proteins.
  • Authors

    Published In

  • Hypertension  Journal
  • Digital Object Identifier (doi)

    Author List

  • Lewis JL; Warnock DG
  • Start Page

  • 491
  • End Page

  • 498
  • Volume

  • 24
  • Issue

  • 4