Species differences in the effect of decreased CSF sodium concentration on salt appetite

During the course of evolution from the beginning of the Caenozoic period, the mammalian species have irradiated into increasingly diverse environments and these physical conditions have imposed powerful selection pressures on the systems of water and salt homeostasis. In the case of physiological actions of hormonal elements of the control systems, effects of antidiuretic hormone and aldosterone on water and salt conservation and of renin-angiotensin II on blood pressure and aldosterone secretion show a general similarity across mammalian species. However, evidence is accruing that there may be large species variation in the vectors of physical, chemical and hormonal changes of the milieu which cause water and salt intake. In the sheep, physiological degree of reduction of CSF [Na] produced by IVT infusion of various hypertonic or isotonic saccharide solutions has a powerful stimulating effect on salt appetite of both Na replete and Na deficient animals. Increasing CSF [Na] reduces appetite. The 0.7 M mannitol CSF infusions initially stimulated thirst but eventually depressed it, presumably due to reduction of CSF [Na]. By contrast, in wild rabbits infusion of 0.9 M mannitol CSF for 2 days at 17 microliter/h caused a large reduction of water intake, a diuresis and no significant increase in salt intake. In laboratory white rats, 0.7 M mannitol CSF infusion at 10 microliter/h for 4 days by Alzet pump, did not increase salt appetite though the infusion was calculated to produce moderate reduction of CSF [Na]. It would appear that there may be significant species differences in effect of reduced CSF [Na] on salt appetite.     

The renin-angiotensin system and sodium appetite

Intracranial renin is a potent stimulus to sodium appetite and thirst, the effects being mediated by local generation of angiotensin II. Intakes are persistent and lead to fluid retention during the first 24 h (Avrith and Fitzsimons, 1983). Increased circulating renin after captopril treatment in adrenalectomized rats (Elfont and Fitzsimons, 1981), or in renal hypertension following partial inter-renal aortic ligation (Costales et al., 1982), also leads to increased intakes of 2.7% NaCl and water. Fluid intakes after aortic ligation were independent of the severity of hypertension produced by this procedure. In both the examples given, additional stimulation resulting from the hypovolaemia itself is required for the full expression of increased sodium appetite, but in both cases angiotensin makes a significant contribution to sodium appetite as well as thirst. Therefore, as has been shown for thirst, angiotensin is one of a number of factors that act together to cause increased sodium appetite in hypovolaemia.     

Parabrachial and hypothalamic interaction in sodium appetite

Rats with bilateral lesions of the lateral hypothalamus (LH) fail to exhibit sodium appetite. Lesions of the parabrachial nuclei (PBN) also block salt appetite. The PBN projection to the LH is largely ipsilateral. If these deficits are functionally dependent, damaging the PBN on one side and the LH on the other should also block Na appetite. First, bilateral ibotenic acid lesions of the LH were needed because the electrolytic damage used previously destroyed both cells and axons. The ibotenic LH lesions produced substantial weight loss and eliminated Na appetite. Controls with ipsilateral PBN and LH lesions gained weight and displayed robust sodium appetite. The rats with asymmetric PBN-LH lesions also gained weight, but after sodium depletion consistently failed to increase intake of 0.5 M NaCl. These results dissociate loss of sodium appetite from the classic weight loss after LH damage and prove that Na appetite requires communication between neurons in the LH and the PBN.     

Sodium transport and salt appetite; the effect of DPH on sodium preference and electrolyte balance in rats

The sodium transport hypothesis of salt appetite asserts thatdrugs affect this appetite according to their effect on sodiumtransport. Sodium appetite was therefore studied in rats treatedwith DPH in order to stimulate sodium transport. During 8 daysof administration by gastric tube rats increased their sodiumintake and preference significantly above control levels involvingintubation with vehicle alone. This response was observed in22 rats offered hypotonic saline (0.5%) and 8 rats offered hypertonicsaline (2%), i.e. solutions to which the rats were normallyneutral or averse. In rats receiving sodium solely in theirfood DPH depressed urinary sodium excretion. The results thussupport the prediction of the hypothesis, namely, that DPH enhancessodium appetite despite its underlying tendency to cause renalsodium retention.     

The dependence of the salt appetite of the rat on the hormonal consequences of sodium deficiency

Richter's discovery of the salt appetite that follows adrenalectomy (1936) raised the question: how does the brain appreciate the need for sodium so that it can mobilize the search for and ingestion of salty substances? It remains unanswered. Recent work suggests that the answer may come from an understanding of the behavioral effects of the hormones of sodium conservation. Fluharty and I have found (Behavioral Neuroscience, 1983) that treatment of salt replete rats with low doses of both angiotensin (Ang II) and a mineralocorticoid (DOCA) evokes a rapid, reliable, and specific appetite for sodium solutions, and we have proposed that the hormones of renal sodium conservation are also the hormones for the behavioral defense against sodium deficiency. We can now report: That the same combined endocrine treatment will compel rats that do not need salt to search for it in a runway. That is, sodium replete rats that have been primed for 3 days with DOCA (500 micrograms/day), which does not produce an appetite for salt, and are then given a pulse intracerebroventricular (ICV) injection of Ang II (60 ng), which by itself does not produce an appetite for salt, will run in an alleyway in order to ingest small drops of 3% NaCl. The hormones act together to make the rat avid for salt and their action is sufficient to drive it to seek salt at a distance and to ingest it at a concentration that untreated rats avoid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of forebrain circumventricular organ ablation on drinking or salt appetite after sodium depletion or hypernatremia

In many previous studies, one or the other forebrain circumventricular organ, the subfornical organ (SFO) or organum vasculosum laminae terminalis (OVLT), was lesioned to test whether it was critical for the behavioral or physiological responses to sodium depletion and hypernatremia. These studies conflict in their conclusions. The present study was designed to create discrete lesions of both the SFO and OVLT in the same animals and to compare these with rats having a lesion of only the SFO or OVLT. Both the OVLT-lesioned group and the combined SFO + OVLT-lesioned group drank significantly more water and saline on a daily basis than Controls or SFO-lesioned rats. In both sodium depletion and hypertonic saline testing, rats with SFO lesions displayed transient deficits in salt appetite or thirst responses, whereas the rats with single OVLT lesions did not. In the sodium depletion test, but not in the hypernatremia test, rats with lesions of both the SFO and OVLT exhibited the largest deficit. The data support the hypothesis that a combined lesion eliminates redundancy and is more effective than a single lesion in sodium depletion tests. The interpretation of the OVLT lesion-only data may have been complicated by a tendency to drink more fluid on a daily basis, because some of those animals drank copious water in addition to saline even very early during the salt appetite test.     

Hormonal regulation of renal sodium and water excretion during normotensive sodium loading in conscious dogs

Saline was infused intravenously for 90 min to normal, sodium-replete conscious dogs at three different rates (6, 20, and 30 micromol x kg(-1) x min(-1)) as hypertonic solutions (HyperLoad-6, HyperLoad-20, and HyperLoad-30, respectively) or as isotonic solutions (IsoLoad-6, IsoLoad-20, and IsoLoad-30, respectively). Mean arterial blood pressure did not change with any infusion of 6 or 20 micromol x kg(-1) x min(-1). During HyperLoad-6, plasma vasopressin increased by 30%, although the increase in plasma osmolality (1.0 mosmol/kg) was insignificant. During HyperLoad-20, plasma ANG II decreased from 14+/-2 to 7+/-2 pg/ml and sodium excretion increased markedly (2.3+/-0.8 to 19+/-8 micromol/min), whereas glomerular filtration rate (GFR) remained constant. IsoLoad-20 decreased plasma ANG II similarly (13+/-3 to 7+/-1 pg/ml) concomitant with an increase in GFR and a smaller increase in sodium excretion (1.9+/-1.0 to 11+/-6 micromol/min). HyperLoad-30 and IsoLoad-30 increased mean arterial blood pressure by 6-7 mm Hg and decreased plasma ANG II to approximately 6 pg/ml, whereas sodium excretion increased to approximately 60 micromol/min. The data demonstrate that, during slow sodium loading, the rate of excretion of sodium may increase 10-fold without changes in mean arterial blood pressure and GFR and suggest that the increase may be mediated by a decrease in plasma ANG II. Furthermore, the vasopressin system may respond to changes in plasma osmolality undetectable by conventional osmometry.     

Reversal of chronic renal hypertension: role of salt and water excretion.

Rats with chronic one-kidney Goldlatt hypertension underwent an unclipping procedure with and without maintenance of body fluid volume through administration of iv salt solution. The blood pressure declined equally in the two groups. It is concluded that external loss of salt and water is not the mechanism for the reversal of this form of hypertension.