THE RENIN-ANGIOTENSIN SYSTEM (RAS) has a central place in this journal because it integrates cardiovascular and renal function in the control of blood pressure and salt and volume homeostasis. The classical controllers of renin release from the kidney are the following. First, the macula densa mechanism, which couples the tubular chloride concentration inversely to the plasma renin concentration (PRC) in the rat (13). Local changes in RAS help determine the sensitivity of the tubuloglomerular feedback mechanism and the set point for autoregulation of renal blood flow (29). Second, the sympathetic nervous system, which stimulates renin secretion through β-adrenergic receptors on the juxtaglomerular cells (6). Third, the pressure-sensitive mechanism for renin release, whose activation in vivo is associated with activation of the sympathetic nervous system (35) and release of hormones, such as oxytocin, which stimulate renin release in rats via a β-adrenergic receptor-dependent mechanism (10, 11).

Mice maintain a constant arterial pressure during alterations in sodium intake by changing the activity of the RAS, and when the RAS is clamped, the blood pressure becomes salt sensitive (5). Technically, it is important that in mice RAS activity is better correlated to PRC than plasma renin activity (PRA). Increasing sodium intake in conscious mice inhibits PRC, plasma ANG II, and aldosterone, but has no effect on PRA (5). In humans, too, a reduction in RAS activity after an oral salt load explains the adaptation of salt excretion to salt intake (1). In addition to its role in long-term salt homeostasis, the RAS defends cardiovascular function in acute hypotension and hypovolemia. Fainting in healthy volunteers after exposure to lower body negative pressure is associated with a sluggish response of the RAS (8). Nitric oxide (NO) promotes salt excretion. Inhibition of NO synthase (NOS) in conscious dogs increases blood pressure and decreases salt and volume excretion independently of renin (25), and NO helps to prevent salt-sensitive hypertension in the Dahl saltresistant rat and decreases salt sensitivity of blood pressure in the Dahl salt-sensitive rat (34). The importance of NO and RAS in pregnancy was emphasized by the demonstration of increased blood pressure in pregnant mice with deletion of the endothelial NOS gene or