Effects of selective angiotensin II and beta1-receptor blockade on renal haemodynamics and sodium handling during orthostatic stress in healthy individuals.

Background: Lower-body negative pressure (LBNP) induces a progressive activation of neurohormonal systems and a renal tubular and haemodynamic response that mimics the renal adaptation observed in congestive heart failure. Both angiotensin II receptor blockers and beta-blockers have been shown to reduce morbidity and mortality in patients with congestive heart failure.

Objective: To investigate whether part of the beneficial effects of angiotensin II receptor blockers and beta-blockers in congestive heart failure is mediated through an improvement in renal haemodynamics and sodium excretory capacity.

Methods and results: The study was performed in healthy normotensive individuals exposed to three levels of LBNP and treated with placebo, 200 mg metoprolol once daily, or 16 mg candesartan once daily, for 10 days. Our results show that candesartan increased renal blood flow, and thereby blunted the vasoconstriction induced by LBNP. This effect was not found with metoprolol. More importantly, both metoprolol and candesartan prevented the sodium retention induced by LBNP, but only candesartan promoted sodium excretion during the 2-h recovery period--that is, once LBNP was interrupted.

Conclusions: These results suggest that blockade of the renin-angiotensin and sympathetic nervous systems in heart failure may be beneficial in part as a result of improved sodium excretion.