Angiotensin II receptor blockade prevents acute renal sodium retention induced by low levels of orthostatic stress

Angiotensin II receptor blockade prevents acute renal sodium retention induced by low levels of orthostatic stress.BackgroundDepending on its magnitude, lower body negative pressure (LBNP) has been shown to induce a progressive activation of neurohormonal, renal tubular, and renal hemodynamic responses, thereby mimicking the renal responses observed in clinical conditions characterized by a low effective arterial volume such as congestive heart failure. Our objective was to evaluate the impact of angiotensin II receptor blockade with candesartan on the renal hemodynamic and urinary excretory responses to a progressive orthostatic stress in normal subjects.MethodsTwenty healthy men were submitted to three levels of LBNP (0, -10, and -20mbar or 0, -7.5, and -15mm Hg) for 1hour according to a crossover design with a minimum of 2days between each level of LBNP. Ten subjects were randomly allocated to receive a placebo and ten others were treated with candesartan 16mg orally for 10days before and during the three levels of LBNP. Systemic and renal hemodynamics, renal sodium excretions, and the hormonal response were measured hourly before, during, and for 2hours after LBNP.ResultsDuring placebo, LBNP induced no change in systemic and renal hemodynamics, but sodium excretion decreased dose dependently with higher levels of LBNP. At -20 mbar, cumulative 3-hour sodium balance was negative at –2.3 ± 2.3mmol (mean ± SEM). With candesartan, mean blood pressure decreased (76 ± 1mm Hg vs. 83 ± 3mm Hg, candesartan vs. placebo, P < 0.05) and renal plasma flow increased (858 ± 52mL/min vs. 639 ± 36mL/min, candesartan vs. placebo, P < 0.05). Glomerular filtration rate (GFR) was not significantly higher with candesartan (127 ± 7mL/min in placebo vs. 144 ± 12mL/min in candesartan). No significant decrease in sodium and water excretion was found during LBNP in candesartan-treated subjects. At –20 mbar, the 3-hour cumulative sodium excretion was + 4.6 ± 1.4mmol in the candesartan group (P = 0.02 vs. placebo).ConclusionSelective blockade of angiotensin II type 1 (AT1) receptors with candesartan increases renal blood flow and prevents the antinatriuresis during sustained lower body negative pressure despite a modest decrease in blood pressure. These results thus provide interesting insights into potential benefits of AT1 receptor blockade in sodium-retaining states such as congestive heart failure.