Inhibition Of Sodium Appetite Research Articles

A possible role for central α2-adrenoceptors on the inhibition of sodium appetite by endotoxin

A possible role for central α2-adrenoceptors on the inhibition of sodium appetite by endotoxin

Local inputs to aldosterone-sensitive neurons of the nucleus tractus solitarius

Aldosterone-sensitive neurons in the nucleus tractus solitarius (NTS) become activated during sodium depletion and could be key neural elements regulating sodium intake. The afferent inputs to these neurons have not yet been defined, but one source may be neurons in the area postrema, a neighboring circumventricular organ that innervates the NTS and exerts a powerful inhibitory influence on sodium appetite [Contreras RJ, Stetson PW (1981) Changes in salt intake after lesions of the area postrema and the nucleus of the solitary tract in rats. Brain Res 211:355–366]. After an anterograde axonal tracer was injected into the area postrema in rats, sections through the NTS were immunolabeled for the enzyme 11-β-hydroxysteroid dehydrogenase type 2 (HSD2), a marker for aldosterone-sensitive neurons, and examined by confocal microscopy. We found that some of the aldosterone-sensitive neurons received close appositions from processes originating in the area postrema, suggesting that input to the HSD2 neurons could be involved in the inhibition of sodium appetite by this site. Axonal varicosities originating from the area postrema also made close appositions with other neurons in the medial NTS, including the neurotensin-immunoreactive neurons in the dorsomedial NTS. Besides these projections, a dense field of neurotensinergic axon terminals overlapped the distribution of the HSD2 neurons. Neurotensin-immunoreactive axon terminals were identified in close apposition to the dendrites and cell bodies of some HSD2 neurons, as well as unlabeled neurons lying in the same zone within the medial NTS. A local microcircuit involving the area postrema, HSD2 neurons, and neurotensinergic neurons may play a major role in the regulation of sodium appetite.

Sodium appetite and Fos activation in serotonergic neurons.

We evaluated serotonergic hindbrain groups of cells for their involvement in the generation and inhibition of sodium appetite. For that purpose, we analyzed the number of Fos-immunoreactive (Fos-ir) cells and double-labeled Fos-serotonin (5-HT)-ir neurons within different nuclei of the hindbrain raphe system and the area postrema (AP). Sodium depletion and sodium appetite were induced by peritoneal dialysis. Twenty-four hours after peritoneal dialysis, a 2% NaCl solution intake test was given to peritoneal dialyzed animals [PD-with access (PD-A) group] and to control dialyzed animals [CD-with access (CD-A) group]. Two additional groups of animals received either peritoneal dialysis or control dialysis but were not given access to the 2% NaCl [CD-no access (CD-NA) group or PD-no access (PD-NA) group]. The number of Fos-ir neurons within different nuclei of the raphe system was increased in spontaneous and induced sodium ingestion of CD-A and PD-A groups compared with the CD-NA and PD-NA groups. The PD-NA group had significantly fewer double-labeled cells along the raphe system compared with the animals in near-normal sodium balance (CD-NA and CD-A) or in the process of restoring sodium balance by consuming NaCl (PD-A). The AP of the PD-A group showed a significant increase in the number of Fos-ir and Fos-5-HT-ir cells compared with the PD-NA and CD groups. Our results suggest that serotonergic pathways with cell bodies in the AP and the raphe system are involved in the control of sodium appetite.

Central lead administration inhibits water intake and sodium appetite in rats.

We have demonstrated that acute third ventricle injections of lead acetate (PbAc) exert a powerful antidipsogenic effect and induce a significant increase in renal sodium excretion. In the present study we confirm the antidipsogenic effect of lead and demonstrate that central administration of this metal, in minute amounts, significantly reduces salt intake both during dehydration and after central angiotensinergic stimulation. Adult male Wistar rats had the third ventricle cannulated seven days before the experiments. During this period they had free access to distilled water and hypertonic saline solution (1.5%). After a 24-h period of fluid deprivation, experimental animals received third ventricle injections of PbAc (0.3, N = 8 and 3.0 nmol/rat, N = 14) while controls received sodium acetate (NaAc; 3.0 nmol/rat, N = 10). Rats treated with PbAc at the highest dose showed a significant reduction (P<0.05) both in water and hypertonic saline intake when compared to controls. When the effect of lead administration on angiotensin II-induced water and salt intake was studied, normohydrated animals received third ventricle injections of angiotensin II (9.6 nmol/rat) after pretreatment with 3.0 nmol/rat of PbAc (experimental group, N = 10) or NaAc (controls, N = 8). The group pretreated with PbAc presented a significant reduction (P<0.05) in both water and salt intake compared to controls. Thus, this study confirms the antidipsogenic effect of central lead injections and demonstrates that the presence of lead in the brain exerts a significant inhibition of sodium appetite.

Central oxytocin mediates inhibition of sodium appetite by naloxone in hypovolemic rats.

Pituitary oxytocin (OT) secretion is inversely related to saline consumption in several experimental models of sodium appetite in rats. Because systemic OT administration does not inhibit sodium appetite, release of OT as a neurotransmitter within the brain, coincident with its secretion from the pituitary, may be related to inhibition of sodium ingestion. The present studies evaluated this possibility by increasing brain OT concentrations both exogenously and endogenously in rats with hypovolemia produced by subcutaneous administration of polyethylene glycol (PEG) solution. Intracerebroventricular (i.c.v.) administration of OT completely abolished intake of 0.5 M NaCl in PEG-treated hypovolemic rats, but did not significantly affect PEG-stimulated water intakes. Endogenous OT secretion was stimulated by systemic treatment with naloxone, which has been shown to increase peripheral and central OT levels. In both one-bottle (0.5 M NaCl) and two-bottle (water and 0.5 M NaCl) drinking tests, intraperitoneal naloxone completely abolished sodium appetite in association with markedly increased pituitary secretion of OT. This inhibition of sodium appetite could be prevented by i.c.v. pretreatment with a specific OT-receptor antagonist, although the antagonist by itself did not affect PEG-stimulated sodium intake. These findings therefore support previous reports which have found that sodium appetite in rats is inhibited by treatments that elicit pituitary release of OT, and provide more direct evidence that brain OT is causally involved in the inhibition of sodium appetite stimulated by such treatments in rats.

Atrial natriuretic peptide inhibits water and sodium intake in rabbits

The effect of atrial natriuretic peptide (ANP) on water and sodium intake was investigated in wild rabbits, a species which does not drink water following i.c.v. or i.v. administration of angiotensin II but develops sodium appetite following i.c.v. infusion of angiotensin II. ANP was given during or after depletion of extracellular fluid volume: hemorrhage, fluid deprivation and administration of furosemide. Systemically administered ANP reduced the water, but not the sodium intake of wild rabbits. I.c.v. administration of ANP inhibited both water and sodium intake. The suppression of thirst following both i.v. and i.c.v. administration of ANP indicates that inhibition of the effect of angiotensin II is not the exclusive mechanism and the circumventricular organs are probably not the exclusive sites of action for ANP. The inhibition of sodium appetite in wild rabbits was consistent with earlier proposals that ANP acts through the inhibition of the effects of angiotensin II. Reduction of food intake coincident with administration of ANP was also noted, but dose-dependent decrease was not observed.