Does whole body autoregulation mediate the hemodynamic responses to increased dietary salt in rats with clamped ANG II?

The present study was conducted to test the hypothesis that salt-dependent hypertension, in rats with an unresponsive renin-angiotensin system, is characterized by a "whole body autoregulation" hemodynamic profile. To test this hypothesis, rats were chronically instrumented to continuously measure cardiac output (CO) and arterial pressure (AP). A venous catheter was implanted for infusion of saline vehicle (Veh; n = 8) or treatment [enalapril (2 mg·kg^-1·day^-1) plus ANG II: ANG-NORM (5 ng·kg^-1·min^-1 ANG II, n = 8) or ANG-HI (10 ng·kg^-1· min^-1 ANG II, n = 9)] to pharmacologically clamp plasma ANG II. After a 10-day recovery period on a 0.1% NaCl diet, AP and CO were measured continuously for 5 days of control (0.1% NaCl), 7 days of high salt (4.0% NaCl), and 5 days of recovery (0.1% NaCl). Hemodynamics did not change in the Veh group at any time. AP increased by ∼20 mmHg in the ANG-NORM and ANG-HI groups when NaCl was increased. Hypertension was mediated by an increase in CO of ∼12% at steady state, with no change in total peripheral resistance (TPR) during the high salt period. AP returned to control levels when dietary sodium was decreased, mediated by a ∼10% decrease in TPR, with CO remaining elevated. There was no difference in the hemodynamic responses to increased salt between the ANG-HI and ANG-NORM groups. We conclude that the whole body autoregulation hypothesis does not explain the hemodynamic profile of salt-dependent hypertension in rats with an unresponsive renin-angiotensin system.