Intraventricular administration of supraphysiological amounts of renin, nerve growth factor preparation, or angiotensin II greatly increased the consumption of water and hypertonic sodium bicarbonate solution by sheep. These effects were antagonized by intraventricular administration of drugs that prevent the formation of angiotensin II or block its receptors. The fact that these angiotensin-blocking drugs did not change the sodium intake of sodium-deficient sheep challenges the idea that central angiotensin action is involved in sodium appetite due to a deficiency.

The role of the renin-angiotensin system (RAS) in the Na appetite of Na-deplete sheep was investigated. Intravenous infusion of the angiotensin-converting enzyme inhibitor, captopril, at 0.01 or 0.1 mg X kg-1 X h-1 did not cause any change in Na intake, although the higher dose caused a marked decrease in mean arterial blood pressure. Intravenous infusion of captopril at 1.0 mg X kg-1 X h-1 over 24 h decreased Na intake by 45-55% in the absence of any change in Na loss. The decrease in Na intake was restored to base-line level or above by concurrent intravenous infusion of angiotensin II (ANG II) at 3.8 or 24 micrograms/h over 24 h but not by intracerebroventricular (ICV) ANG II at 3.8 micrograms/h. In addition, ICV infusion of 0.7 M mannitol (1 ml/h over 3 h), which reduced cerebrospinal fluid (CSF) and brain extracellular fluid [Na], still increased Na intake when combined with intravenous captopril. Water intake was not altered during intravenous captopril or ANG II alone but was increased during ICV ANG II or 0.7 M mannitol (with or without iv captopril). In conclusion, these results suggest that the RAS is involved in the Na appetite of the Na-deplete sheep. Furthermore, it would appear that the brain area involved is one without a blood-brain barrier but with a CSF-brain barrier, such as one of the circumventricular organs. Also, it would appear that the effect of lowered cerebral Na and the effect of activation of the renin-angiotensin system on Na appetite are independent.

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Infusions (20 microliters/min) of isotonic (0.27 M) mannitol dissolved in Na-free artificial cerebrospinal fluid (CSF) were made for 2 h into the lateral cerebral ventricle (IVT) of conscious 68 h dehydrated sheep. The IVT infusion induced a conspicuous drop in renal sodium excretion and marked rise in plasma renin concentration (PRC). The antinatriuretic response to the IVT infusion was not altered by the intravenous administration of ADH or te converting enzyme blocker (SQ 14225, Captopril). Surgical bilateral renal denervation did not change the antinatriuretic response while the increase in PRC was extinguished. Samples of CSF were collected prior to, and 15 min after the end of the infusion. These showed a reduction in CSF [Na], while CSF osmolality remained unchanged. The study supports the view that sodium sensitive receptors close to the cerebral ventricular system participate in the regulation of renal sodium excretion and renin release, it also suggests that renal sodium excretion is affected by an unknown hormonal factor of cerebral origin, while the release of renin seen in response to a reduction in CSF [Na] is mediated by the renal nerves.