Distinct rapid and slow phases of salt-induced hypertension in Dahl salt-sensitive rats

Abstract

To test the hypothesis that Dahl salt-sensitive (Dahl-S) rats exhibit distinct and separable phases of salt sensitivity. Blood pressure (BP) telemetry was used to describe the detailed time course of salt-induced hypertension in Dahl-S rats and in hybrid rats derived from Dahl-S and Dahl salt-resistant strains. Switching to a high salt (4% NaCl) diet led to a biphasic increase in BP. Phase-1 reached a plateau in 4 days whereas phase-2 progressed slowly over the subsequent 5 weeks. In hybrid rats, phase-1 was present in each rat whereas phase-2 was absent in many individuals. A correlation of the amplitude of the first and second phases was of borderline significance in Dahl-S rats (P = 0.053, R2 = 0.44, n = 9) but was clearly significant in hybrid rats (P < 0.0001, R2 = 0.78, n = 22). Increases in BP were reversible following 1 week of high salt but progressively less so after 4 and 7 weeks. Estimation of the chronic pressure-natriuresis relationship suggests that phase-1 is attributable to a reduced slope of this relationship. In contrast, phase-2 corresponds with a further reduction in slope and a progressive and irreversible resetting of the relationship to higher BP levels. Two phases of salt sensitivity coexist and provide distinct contributions to salt-induced hypertension in Dahl-S rats. Our data also suggest that short-term measures of salt-sensitivity may be predictive of the effect of salt on the eventual progression of salt-induced hypertension.