Presystemic signals in the control of thirst, salt appetite, and vasopressin secretion.

Presystemic signals play an important role in the control of ingestive behavior by allowing animals to anticipate imminent physiological changes. The significance of such signals in the control of food intake has been amply demonstrated and is widely appreciated. Our recent experiments have revealed that presystemic signals also provide important early feedback when rats drink water or NaCl solution, before the ingested fluids are absorbed and influence cerebral osmoreceptors or cardiovascular baroreceptors. These early signals clearly affect vasopressin (VP) secretion and thirst. They relate either to the distension of the stomach and proximal small intestine (presumably mediated by local stretch receptors) or to the concentration of fluid that empties from the stomach into the small intestine (presumably mediated by visceral osmo- or Na(+)-receptors). Dehydrated dogs use functionally comparable signals from the oropharynx while drinking in order to inhibit both VP secretion and thirst. However, that system differs in several respects from the system in rats aside from the fact that the presystemic signals in rats are not oropharyngeal: in rodents, (a) separate early signals influence VP secretion and thirst, (b) early signals can provide both stimulation and inhibition of VP secretion and thirst, and (c) the early signals are associated with both the volume and concentration of ingested fluid. These presystemic signals also inhibit the intake of NaCl solution by rats with salt appetite.

Inhibition of NaCl appetite when DOCA-treated rats drink saline.

Marked increases in the consumption of concentrated NaCl solution were elicited in rats by daily injection of the synthetic mineralocorticoid, deoxycorticosterone acetate (DOCA). DOCA-treated rats drank different volumes of NaCl solution depending on its concentration (between 0.15 M and 0.50 M), with less consumed (in milliliters) the more concentrated the fluid was. In consequence, total Na(+) intake (in milliequivalents) was roughly similar in all groups. Gastric emptying of Na(+) also diminished as the concentration of the ingested NaCl solution increased, and the delivery of Na(+) to the small intestine was remarkably similar in all groups. Cumulative volume of ingested fluid in the stomach and small intestine was very closely related to intake (in milliliters) of the concentrated NaCl solutions. Systemic plasma Na(+) levels did not increase until after rats stopped consuming concentrated NaCl solution, although they were elevated at the onset of water ingestion. The situation appeared to be different when 0.15 M NaCl was consumed. This isotonic solution emptied and was absorbed relatively rapidly, and DOCA-treated rats drank larger amounts of it throughout a 1-h test period than when they drank concentrated NaCl solutions. Collectively, these findings suggest that saline consumption by DOCA-treated rats may be inhibited by two presystemic factors, one related to the volume of ingested fluid (i.e., distension of the stomach and small intestine) and one related to its concentration (i.e., elevated osmolality of fluid in the small intestine and/or in adjacent visceral tissue).

Control of thirst and salt appetite in rats: early inhibition of water and NaCl ingestion.

Most previous studies on the controls of thirst and salt appetite in rats have focused on systemic factors. Our recent experiments suggest that presystemic factors also are likely to play an important role. For example, dehydrated rats were found to consume similar volumes in an initial drinking bout when given access either to water or 0.05, 0.10, 0.15, or 0.20 M NaCl solution. Thus, cessation of the bouts evidently was not related to the concentration of fluid consumed but to its volume. It occurred despite the continued presence of known systemic stimuli for thirst (i.e. either increased plasma osmolality or decreased plasma volume), and therefore it resulted from inhibition rather than satiation. This inhibition appeared to derive from signals related to the cumulative volume of ingested fluid in the stomach and small intestine. Similar findings were obtained in studies of NaCl solution intake by NaCl-deprived adrenalectomized rats. These and other observations suggest that gastrointestinal fill generates stimuli that inhibit drinking in rats regardless of whether thirst or salt appetite motivates fluid consumption and regardless of whether rats consume water or NaCl solution.

Water ingestion by rats fed a high-salt diet may be mediated, in part, by visceral osmoreceptors.

After surgical removal of all salivary secretions ("desalivation"), rats increase their consumption of water while eating dry laboratory chow. In the present experiments, desalivated rats drank even more water while they ate "powdered" high-salt food (i.e., <15-mg food particles). The Na+ concentration of systemic plasma in these animals was not elevated during or immediately after the meal, which suggests that cerebral osmoreceptors were not involved in mediating the increased water intake. A presystemic osmoregulatory signal likely stimulated thirst because the Na+ and water contents of the gastric chyme computed to a solution approximately 150 mM NaCl. In contrast, desalivated rats drank much smaller volumes of water while eating "pulverized" high-salt food (i.e., 60-140-mg food particles), and the fluid mixture in the gastric chyme computed to approximately 280 mM NaCl solution. These and other findings suggest that the NaCl ingested in the powdered high-salt diet was dissolved in the gastric fluid and that duodenal osmoreceptors (or Na+-receptors) detected when the concentration of fluid leaving the stomach was elevated after each feeding bout, and promptly stimulated thirst, whereupon rats drank water until the gastric fluid was diluted back to isotonicity. However, when rats ate the pulverized high-salt diet, much of the NaCl ingested may have been embedded in the gastric chyme and therefore was not accessible to visceral osmoreceptors once it emptied from the stomach. Consistent with that hypothesis, fluid intakes were increased considerably when desalivated rats drank 0.10 M NaCl instead of water while eating either powdered or pulverized high-salt food.

Inhibition of thirst when dehydrated rats drink water or saline.

The present experiments sought to identify the physiological signals that inhibit thirst when dehydrated rats drink water or NaCl solution. Rats were deprived of drinking fluid but not food overnight. When allowed to drink again, the dehydrated animals consumed water or saline (0.05 M, 0.10 M, 0.15 M, or 0.20 M NaCl solution) almost continuously for 5-8 min before stopping. The volumes consumed were similar regardless of which fluid they ingested, but blood analyses indicated that increased plasma osmolality and decreased plasma volume, or both, still remained when drinking terminated. These results suggest that the composition of the ingested fluid is less significant than its volume in providing an early signal that inhibits thirst and fluid consumption by dehydrated rats. Analyses of the gastrointestinal tracts revealed that the cumulative volume in the stomach and small intestine correlated highly with the amount consumed regardless of which fluid was ingested. These and other results suggest that the volume of fluid ingested by dehydrated rats is sensed by stretch receptors detecting distension of the stomach and small intestine, which provide an early inhibitory stimulus of thirst.

Inhibition of vasopressin secretion when dehydrated rats drink water.

The present study determined whether vasopressin (VP) secretion is inhibited by an oropharyngeal signal associated with swallowing fluids when dehydrated rats drink water, as it is when dehydrated dogs are used as experimental subjects (Thrasher, TN, Keil LC, and Ramsay DJ. Am J Physiol Regul Integr Comp Physiol 253: R509-R515, 1987). VP levels in systemic plasma (pVP) fell rapidly when rats drank water after overnight water deprivation. Systemic plasma Na+ concentration (pNa) also fell, but that change likely contributed little to the early inhibition of VP secretion. In contrast, consumption of water by dehydrated rats with an open gastric fistula had no effect on pVP, nor did consumption of isotonic saline by dehydrated rats; in neither case was pNa affected by fluid consumption. These findings provide no evidence that the act of drinking inhibits VP secretion in dehydrated rats. Thus some post-gastric effect of the ingested water seems to be responsible for the inhibitory signal. These results are consistent with previous suggestions that an early inhibitory stimulus for VP secretion in rats is provided by post-gastric visceral osmo- or Na+ receptors that sense the composition of the ingested fluid.

Increased water intake by rats maintained on high NaCl diet: analysis of ingestive behavior.

To determine the temporal relation between the ingestion of dry food containing 8% NaCl and the increased daily consumption of water that occurs when rats eat this diet, rats were placed in specially designed cages linked to microprocessors that allowed the continuous monitoring of food and water ingestion. The increase in water intake was found to result from increases both in number and size of individual drinking bouts. Approximately 75% of the water intake was consumed in drinking bouts that occurred less than 5 min after feeding. Indeed, rats rarely consumed 8% NaCl diet without also drinking water in the same ingestive episode, and the volume of water they drank was proportional to the food intake in that episode. These and other observations suggest that ingestion of the high salt diet stimulated thirst rapidly. As such, they are consistent with previous reports that visceral osmoreceptors (or Na(+)-receptors) detect osmolytes passing through the gastrointestinal tract and provide an early stimulus of thirst in rats that precedes large increases in systemic plasma osmolality.