Membrane ion transport in erythrocytes of salt hypertensive Dahl rats and their F2 hybrids: The importance of cholesterol

Abstract

The possible association of salt hypertension and altered lipid metabolism with abnormalities of particular systems transporting sodium and potassium has been studied in erythrocytes of Dahl rats and their F2 hybrids fed a high-salt diet since weaning. Our attention was paid to the Na+-K+ pump, Na+-K+ cotransport and especially to passive membrane permeability for Na+ and Rb+ (Na+ and Rb+ leak), because the Na+ leak was found to be dependent on the genotype, age and salt intake of Dahl rats, whereas the Rb+ leak was suggested to be a potential marker of salt sensitivity in Dahl and Sabra rats. Young male Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats kept on a low-salt (0.3% NaCl) or high-salt diet (8% NaCl) were used for the progenitor study. The subsequent genetic study was based on 135 young male SS/Jr×SR/Jr F2 hybrids fed a high-salt diet since weaning. Ouabain (5 mmol/l) and bumetanide (10 μ mol/l) were used to distinguish the contribution of the Na+-K+ pump, Na+-K+ cotransport and passive membrane permeability to measured net Na+ fluxes and unidirectional Rb+ (K+) movements. Compared to normotensive SR/Jr animals, salt-loaded SS/Jr rats had higher blood pressure (BP), elevated erythrocyte Na+ content, and increased Na+ and Rb+ leaks together with enhanced Na+ and Rb+ transport mediated by the Na+-K+ pump and Na+-K+ cotransport system. Salt hypertensive Dahl rats were also characterized by elevated plasma levels of total cholesterol and triglycerides, which were positively associated with BP of F2 hybrids (r=0.27 and 0.24, p<0.01). In F2 hybrids, mean arterial pressure correlated significantly with erythrocyte Na+ content (r=0.24, p<0.01 and ouabain-sensitive Na+ extrusion, but not with the passive membrane permeability for Na+ or Rb+ (r=-0.02 and 0.06, not significant). Both of the above-mentioned significant associations could partially be ascribed to the dependence of erythrocyte Na+ content and ouabain-sensitive Na+ extrusion on plasma cholesterol (r=0.18 and 0.21, p<0.05). Our results support the idea that abnormal lipid metabolism and/or altered Na+,K+-ATPase function play an important role in the pathogenesis of salt hypertension in salt-sensitive Dahl rats.