BRAIN ANGIOTENSINERGIC PATHWAYS MEDIATE RENAL NERVE INHIBITION BY CENTRAL HYPERTONIC NACL IN CONSCIOUS SHEEP

The renal sympathetic responses to infusion of hypertonic solutions in to the lateral cerebral ventricles were investigated in conscious shee p. Intracerebroventricular infusion of artificial cerebrospinal fluid (CSF) containing 0.6 M NaCl, at 1 ml/h for 20 min, reduced renal sympa thetic nerve activity (RSNA) by 81 +/- 5% (n = 6, P < 0.001). Plasma r enin concentration also fell (P < 0.05), whereas arterial pressure inc reased by 6.4 +/- 0.7 mmHg (P < 0.01). Intracerebroventricular hyperto nic sorbitol (0.9 M in CSF at 1 ml/h) had no effect. The AT(1) recepto r antagonist losartan (1 mg/h) abolished the plasma renin and arterial pressure responses to intracerebroventricular hypertonic saline and s ignificantly reduced the fall in RSNA to 17 +/- 10% (P < 0.001). Durin g intracerebroventricular hypertonic saline, the baroreflex relation o f RSNA to diastolic pressure was shifted to the left and that to centr al venous pressure was abolished compared with control relations obtai ned by manipulating pressure with intravenous phenylephrine. These fin dings indicate that 1) RSNA is inhibited by a central mechanism that s enses high sodium (or perhaps chloride) concentration rather than hype rtonicity; 2) this inhibition occurs independently of reflexes from hi gh-and low-pressure baroreceptors, although these may enhance the inhi bition; and 3) inhibition of RSNA by hypertonic saline involves a cent ral angiotensinergic pathway.