Central oxytocin inhibition of salt appetite in rats: evidence for differential sensing of plasma sodium and osmolality.

Abstract

Sodium chloride ingestion is stimulated during conditions of sodium deficiency to maintain body fluid and electrolyte balance. Recent studies have indicated that salt appetite in rats is often inversely related to peripheral and central secretion of the hormone oxytocin (OT). We studied the potential role of central OT on salt and water ingestion by treating rats intracerebroventricularly with OT conjugated to the A chain of the plant cytotoxin ricn (rAOT) to produce a chronic selective inactivation of brain ceils containing OTreceptive elements. The rats treated with rAOT and control rats treated with the ricin A chain alone were given 5-hr two-bottie (water and 0.5 M NaCI) drinking tests 30 min after they were made hyperosmolar by injections of hypertonic (2 M) mannitol solution, which elevated plasma osmolality but reduced plasma Na+ concentration. In the control rats only water intake was stimulated in response to the induced hyperosmolality, but in the rAOT-treated rats hypertonic mannitol caused a robnst salt appetite as weil as thirst. Analogous results were obtained in rats treated with two different OT-receptor antagonists prior to induction of hyperosmolality with mannitol. In contrast to these results, when hyperosmolalibty was induced by inistration of equivalently hypertonic (1 M) NaCI, which elevated both plasma osmolality and plasma Na4 concentration, only water intake but not salt intake was stimulated in both control and OT-receptor antagonist-treated rats. When salt appetite was stimulated by the physiological stimulns of polyethylene glycol-induced hypovolemia, hypertonic mannitol simiary inhibited salt ingestion in control animals but not in rAOT-treated rats, whereas hypertonic NaCl inhibited subsequent salt ingestion in both groups. These results suggest that salt appetite is regulated by both Na+-and osmolality-sensing mechanisms in rats. In addition, they indicate that central OT likely mediates a significant component of osmolality-related inhibition ofsalt appetite but does not appear to be essential for Na+-related inhibition of this important homeostatic behavior.Salt appetite is a vital homeostatic behavior in many species. The ingestion of salt in response to a perceived body deficit of Na+ is analogous to the ingestion of water by dehydrated animals. Together these two behaviors promote maintenance of body fluid and electrolyte balance within very narrow limits. In rats, ingestion of concentrated NaCl solutions can be induced by diverse experimental manipulations. However, regardless of the paradigm employed, NaCl ingestion is generally most prominent when pituitary oxytocin (OT) release is either low or at basal levels and is almost always inhibited when OT release is stimulated (1). Since central, but not peripheral, administration of OT can inhibit salt appetite in rats, it has been proposed that OT pathways projectingThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accorda...

Salt Appetite and the Renin-Angiotensin System

“…21 These results are supportive of studies in rats that showed that PEG-induced salt intake was inhibited by central OT administration, 9 whereas lesions of the brain OT system increased the response to hyperosmolality. 11 In contrast, an OT antagonist had no effect on PEGinduced salt intake. 9 Studies that compared the effect of volume expansion with hypertonic mannitol versus saline showed that saline intake was responsive to osmolality changes, rather than sodium.…”

“…9 Studies that compared the effect of volume expansion with hypertonic mannitol versus saline showed that saline intake was responsive to osmolality changes, rather than sodium. 11 To proceed to the next stage, we determined whether a stimulus to volume receptors alters salt intake in mice and whether the response is changed in the OT gene-disruption model. Volume depletion with PEG has become a standard test model.…”

“…9,10 There is also evidence for an OT-specific response to increased osmolality, rather than sodium. 11 A role for central angiotensin II (Ang II) in mediating the OT responses was suggested, because OT antagonists potentiated the salt intake induced by Ang II. 12,13 In addition, central administration of Ang II provoked systemic release of OT 14,15 and vasopressin 14 -16 in rats.…”

Role of the lateral parabrachial nucleus in the control of sodium appetite

“…Oxytocin release in the brain seems to parallel the secretion of this hormone into the blood, and oxytocin in both systems is activated by similar stimuli, including ANG II (12,45,46,123). However, the oxytocin found and released in the CNS inhibits sodium appetite (12)(13)(14)(121)(122)(123)(124). Intracerebroventricular (icv) injections of oxytocin reduce sodium intake (12)(13)(14), and central delivery of an oxytocin receptor antagonist, or the destruction of brain neurons containing oxytocin receptors by oxytocin conjugated to the cytotoxin ricin, increase hypertonic NaCl intake in rats treated with a central injection of ANG II (12,123).…”

“…In contrast, blood volume expansion releases humoral factors, such as atrial natriuretic peptide (ANP), which inhibit salt and water intake (5,6,14,49). Other agonists and receptor subtypes, such as oxytocin and ␣ 2 -adrenoceptors, act in the brain to inhibit behavioral responses that expand body fluids (12,13,39,40,48,93,123,125).ANG II and hyperosmolarity act on sites that function as sensory structures, specifically the OVLT, SFO, and AP, which are located outside the blood-brain barrier. In some cases they also act on structures located within the blood-brain barrier such as the supraoptic nucleus of the hypothalamus (25, 26, 75-77, 84, 86, 118, 119).…”