Dopamine modulation of prolactin and vasopressin but not behavior on satiation of sheep.

We have investigated the rapid changes in plasma prolactin and arginine vasopressin (AVP) associated with water satiation in ruminants. Sheep deprived of water for 72 h were allowed voluntary access to ad libitum water. Each sheep drank approximately 5 liters in a single draft. This was performed in a head-down position, which was maintained for approximately 2-3 min and ceased rapidly with an abrupt movement to the upright position. During dehydration, plasma sodium, osmolality, and AVP all increased significantly, but prolactin was unaffected. On rehydration, AVP fell to basal levels within 5 min, but prolactin increased as a short pulse, after which it rapidly fell again. Plasma sodium and osmolality returned to predehydration levels within 6 h of satiation. A possible role of dopaminergic mechanisms in these responses was investigated by the administration of the dopamine agonist bromocriptine or the antagonist metoclopramide. Neither of these agents had any observable effects on the drinking behavior of the sheep during water satiation. During metoclopramide treatment, dehydration was associated with a marked fall in prolactin, and on rehydration there was a prompt and very marked increase in prolactin level. There was also an exaggerated increase of AVP during dehydration and a decrease on rehydration. Bromocriptine had relatively little effect on prolactin responses but prevented the drinking-associated inhibition of AVP, demonstrating an unexpected dissociation between AVP secretion and the stereotyped drinking response.

Relation of endogenous systemic and brain angiotensin II, arginine vasopressin and prolactin with the genesis of salt appetite in cattle.

Angiotensin II (AII), arginine vasopressin (AVP) and prolactin (PRL) were measured by radioimmunoassay in plasma and cerebrospinal fluid (CSF) in concurrent daily samples from conscious unrestrained steers. Packed cell volume, [Na+] and osmolality were also measured from these samples. Salt appetite was assessed during a 5-min daily session of operant conditioning. Food and water was always available. Unilateral parotid duct fistulation was effected under xylazine analgesia and halothane/O2 anaesthesia. To prevent a sodium deficit developing from loss of [Na+] in the extruded saliva, 0.3 M NaHCO3 was available ad libitum so that each animal could ingest sufficiently to balance the salivary loss. A week later epidural cannulae were implanted in the cisternae magna using the same anaesthesia. Three days afterwards when the saliva [Na] was 78 mmol/1, the 0.3-M NaHCO3 supplement was withdrawn for 7 days so that sodium deficiency developed to a degree which evoked salt appetite. When the NaHCO3 supplement was restored ad libitum, all aspects of [Na+] deficiency and salt appetite were completely ameliorated within 2-3 days. Packed cell volume increased and body weight decreased (p less than 0.05) during depletion, but rapidly returned to normal on day 2 of repletion. Both plasma and CSF osmolality were reduced during depletion as were plasma [Na+] (p less than 0.01) and CSF [Na+] (p less than 0.001). From a basal value of 64.7 +/- 9.35 fmol/ml on day 0, plasma AII increased to 229.2 +/- 46.65 fmol/ml (p less than 0.001) on day 3, prior to the onset of salt appetite on days 4-7. In marked contrast to plasma AII during sodium depletion, CSF AII was unchanged during salt appetite. There was no correlation between plasma and CSF AII during behavioural salt appetite.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutrient sensitivity of gastric emptying of digesta in the preruminant calf.

1. Studies of gastric function were made in preruminant calves fitted with a single abomasal cannula, re-entrant cannulas in the duodenum close to the pylorus and recording electrodes on the pyloric antrum and proximal duodenum. 2. Simultaneous measurements were made of gastric emptying of a saline (9 g sodium chloride/l) meal, myoelectric activity of antral muscle and plasma concentration of somatostatin in jugular blood whilst infusing the duodenum with different solutions. The duodenal infusates were isotonic sodium bicarbonate (300 mosmol/kg), hyperosmolar solutions of NaCl (1000 mosmol/kg), sodium carbonate (500 mosmol/kg), sucrose (1000 mosmol/kg), 41 g emulsified butterfat/kg or 60 mM-hydrochloric acid. 3. Infusing the duodenum with isotonic NaHCO3 stimulated intense myoelectric activity of the antral smooth muscle and rapid emptying of the test meal. In contrast, infusions of 60 mM-HCl reduced antral motility and inhibited gastric emptying of digesta. This inhibitory response to HCl infusion was related to a significant (P less than 0.05) increase of somatostatin in peripheral venous blood. 4. The Na2CO3 infusate, like HCl, inhibited gastric motor activity and digesta emptying, but the concentration of circulating somatostatin was only slightly elevated above pre-infusion levels. 5. Compared with the effects of infusing HCl, infusions of emulsified butterfat or hyperosmolar NaCl and sucrose induced a greater intensity of antral motor activity and faster outflow of gastric effluent, although not to the same extent as with isotonic NaHCO3. However, as with isotonic NaHCO3, these infusates did not evoke the release of somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)

The coincidental effects of dehydration and rehydration on plasma and cerebrospinal fluid angiotensin II levels in unrestrained steers.

Changes in plasma (pAII) and cerebrospinal fluid (csf AII) immunoreactive angiotensin II have been measured in 6 unrestrained steers during dehydration and rehydration. Prior to dehydration, plasma osmolarity (pOsm) was 301.3 +/- 0.62 mOsm/l (mean +/- S.E.M.) and on dehydration progressive elevation of pOsm developed so that after 4 days it was 338.5 +/- 3.00 mOsm/l (P less than 0.001). Packed cell volume was elevated during dehydration from 39.9 +/- 0.64% to 44.7 +/- 1.24% (P less than 0.001). Radioimmunoassay (RIA) of pAII indicated a similar pattern of progressive elevation during dehydration when after 4 days pAII had risen from 54.7 +/- 11.6 fM/ml to 177.6 +/- 18.4 fM/ml (P less than 0.001). RIA of csf AII, however, indicated no complementary pattern of change during dehydration, the only significant alteration from basal levels of 166.0 +/- 13.2 fM/ml occurred after 2 days when csf AII was reduced to 83.1 +/- 14.5 fM/ml (P less than 0.01). Antiserum specificity tests indicated that some of the csf AII could have been due to metabolites of AII, and high performance liquid chromatographic separation of angiotensin peptides in csf suggested that the major contributants were AII and AIII. These analogues which may have central neural effects were not consistently elevated during dehydration of cattle. It is concluded therefore, that the role of angiotensin in central neural mechanisms of fluid balance in dehydrated animals depends primarily on the systemic renin-angiotensin system and not an endogenous brain renin-angiotensin system.

Aspects of ingestive behavior in cattle.

Ingestive behavior in cattle differs from other species because of physiological mechanisms developed pari passu with fermentative digestion. The secondary refection of rumination allows remastication and reinsalivation of the large bulk of vegetable food ingested. The need to buffer acid products of cellulose digestion demands continuous high secretion of alkaline saliva. Nervous and hormonal stimuli emanating from the gastrointestinal tract evoke centrally controlled behavior of hunger and satiety. The four primary taste receptors occur in cattle but thresholds are low. Because of the low Na level in plants, cattle have developed the behavior of seeking salt by taste and smell. During Na deficiency it can be shown that cattle readily learn and develop memory, providing a powerful behavioral dimension in the search for food.

Vasopressin in plasma and cerebrospinal fluid of hydrated and dehydrated steers.

Levels of arginine-vasopressin (AVP), the antidiuretic hormone, have been concurrently measured by radioimmunoassay (RIA) in plasma (p) and cerebrospinal fluid (CSF) from conscious, unrestrained steers. During 4 days of dehydration, plasma osmolarity (posm) rose progressively from control hydrated levels of 301.3 +/- 0.632 mosm/1(mean +/- SE) to 338.5 +/- 3.090 mosm/1(p less than 0.001). Packed cell volume also rose from 39.9 +/- 0.64% to 44.7 +/- 1.24% (p less than 0.001). Associated with these changes was a progressive increase in pAVP from control levels of 1.3 +/- 0.19 microU/ml to 16.9 +/- 1.88 microU/ml(p less than 0.001) after 4 days without water. Log pAVP was linearly related to posm (r = 0.82, p less than 0.001). Mean level of CSF-AVP in control animals was 5.4 +/- 0.97 microU/ml. During dehydration, CSF-AVP levels also rose, becoming significantly greater than control levels (p less than 0.01) after 3 days without water and further increasing to reach 15.2 +/- 1.83 microU/ml after 4 days without water (p less than 0.001). Log CSF-AVP could also be linearly related to posm (r = 0.62, p less than 0.01). Termination of dehydration by restoration of ad libitum water supply was accompanied by return of pAVP and CSF-AVP to pre-dehydration levels. Regression analysis of concurrent levels of pAVP an CSF-AVP indicates that CSF-AVP levels are linearly correlated to pAVP levels in hydrated and dehydrated animals (r = 0.70, p less than 0.001). These experiments suggest that neurosecretory neurons secreting AVP at sites accessible to CSF respond to similar stimuli during dehydration as those neurons secreting AVP into blood.

Plasma prolactin during the body fluid and electrolyte changes of dehydration and sodium depletion in steers.

The effect of dehydration and sodium depletion on plasma prolactin levels in steer calves is very different from the changes seen in the rat and possibly in man. Removal of drinking water was followed by progressive dehydration for 96 h during which time packed cell volume (PCV) increased from 39.9% to 44.7% and plasma osmolarity (pOsm) rose from 303.3 mOsm to 342.0 mOsm/l with hypernatraemia. At the same time plasma prolactin ( pPRL ) was rapidly reduced from a basal value of 2.3 ng/ml to barely measurable amounts and remained low during dehydration. Restoration of ad lib drinking water was followed by rapid reduction of PCV and pOsm to sub-basal levels during which time the pPRL increased significantly to persist at 15 ng/ml. Sodium depletion was produced by continuous loss of sodium-rich saliva from unilateral fistulation of a parotid duct. During sodium deficiency PCV increased from 38.6% to 45.6% but pOsm fell significantly from 299.9 mOsm/l to 286 mOsm/l with hyponatraemia. As in dehydration, during sodium depletion pPRL was suppressed, and after 7 days was reduced from a basal level of 5.4 ng/ml to 0.5 ng/ml. The sodium depleted steers when given 0.3M NaHCO3, which they consumed readily to restore sodium homeostasis, restored the deficiency gradually in 5 days when pPRL , pOsm and PCV all returned to basal levels without any 'overshoot' or hypersecretion of pPRL . Our finding indicate that extracellular fluid volume changes, not electrolyte content, affect pPRL . This is in agreement with results obtained in the rat, and possibly in man, but the fact that in the steer, the endogenous changes in prolactin level show a profound reduction provides an extreme example of species difference. The means whereby both divergent physiological processes of dehydration and sodium depletion generate stimuli which inhibit prolactin secretion and the relevance of this response in fluid balance homeostasis requires further research.

The olfactory detection of sodium and lithium salts by sodium deficient cattle.

With development of Na+ depletion in cattle enhancement in the specific ability to smell very low concentrations of salt occurs. At the same time a behaviour pattern develops, in which increased locomotory activity is seen, directed towards searching for sodium salts. Following the initial successful location of a sodium source the pattern once learned, is consolidated by repetition and by consummation of the salt reward. Our data shows that olfactory and gustatory receptors are able to detect minute amounts of sodium salts as biochemical disruption develops with Na+ depletion but the central input from smell and taste receptors remain distinct. Salt appetite does not appear to be pleasurable (hedonic) in cattle, for salt appetite which is a feature of Na+ depletion does not persist when the ionic deficit is restored. The innate behaviour which develops with increased salt appetite in cattle may account for the evolutionary success and worldwide distribution of ruminants.

Differential effect of acid meals on abomasal emptying and secretion in the milk-fed calf.

Preruminant (milk-fed) calves were prepared with an abomasal and re-entrant duodenal cannulae to assess the effect of acid test meals on abomasal emptying and secretion. Isotonic saline meals acidified with hydrochloric acid to pH 2 instilled directly into the abomasum did not affect abomasal emptying or acid and pepsin secretion when compared with saline meals at pH 6. Isotonic saline meals at pH 1.2 significantly inhibited abomasal acid secretion, but had little effect on emptying or pepsinogen secretion. Abomasal emptying, acid secretion and pepsinogen secretion were significantly inhibited when acid was introduced into the duodenum, irrespective of the acidity of the test meal. It is concluded that in the calf acid meals inhibit gastric acid secretion alone without effect on pepsinogen secretion and abomasal emptying. All three abomasal functions, however, were inhibited by acidification of the duodenum.

Intestinal control of gastric function in the calf: the relationship of neural and endocrine factors.

1. Gastric emptying and secretion were measured in conscious calves during alkaline or acid perfusion of the duodenum with simultaneous assessment of endogenous plasma somatostatin, gastrin and blood 5-hydroxytryptamine (5-HT).2. Alkaline duodenal perfusion (isotonic NaHCO(3)) caused rapid gastric emptying and increased gastric acid secretion without any affect on basal levels of somatostatin, 5-HT or gastrin.3. Duodenal perfusion of 60 mm-HCl caused complete inhibition of gastric emptying, reduced gastric acid secretion considerably, and an associated elevation of somatostatin basal levels from 123.8 +/- 11.2 to 281.9 +/- 23.0 pg/ml. (P < 0.01) occurred.4. These effects of duodenal perfusion were unimpaired by bilateral lumbar splanchnectomy.5. On bilateral cervical vagotomy of the splanchnectomized calves, the inhibition of gastric function evoked by duodenal acidification persisted, and plasma somatostatin showed a further significant elevation to 506.9 +/- 49.9 pg/ml. (P < 0.01) but gastrin and 5-HT remained unchanged. The increased gastric function caused by alkaline duodenal function was significantly reduced following vagotomy but basal somatostatin, gastrin and 5-HT in the blood remained unaffected.6. These results suggest that the stimulatory effect on gastric emptying and acid secretion of isotonic NaHCO(3) in the duodenum may be mediated, partially at least, through the vagal nerves but not the splanchnics.7. The complete inhibition of gastric function which ensued on acidification of the duodenum and which continues after splanchnovagotomy, is not mediated by the autonomic nervous system. This inhibitory process appears to involve the endocrine system only, with somatostatin (but not gastrin or 5-HT) fulfilling a main enterogastrone role.

Correlation of endogenous somatostatin, gastric inhibitory polypeptide, glucagon and insulin with gastric function in the conscious calf.

Levels of endogenous somatostatin, gastric inhibitory polypeptide (GIP), glucagon and insulin were measured during gastric (abomasal) emptying in the conscious calf. Isotonic NaHCO3 infused into the duodenum increased rates of emptying of a saline test meal and of gastric acid secretion, but had no effect on basal levels of blood glucose, somatostatin, GIP, insulin or glucagon. By contrast, intraduodenal infusion of 60 mM-HCl caused complete inhibition of gastric emptying, reduction of acid secretion, and an immediate increase in plasma somatostatin from 121.3 +/- 9.4 (S.E.M.) to 286.3 +/- 16.3 pg/ml (P less 0.01) but levels of GIP, insulin, glucagon and glucose were unaltered. Intravenous injection of somatostatin (0.5 microgram/kg) suppressed the antral electromyographic recording and gastri efflux so long as plasma somatostatin levels remained above approx. 200pg/ml. This suggest that somatostatin can be released by intraduodenal acidification and that it inhibits gastric function by an endocrine effect. Since somatostatin retards gastric emptying it may therefore have an indirect role in nutrient homeostasis by limiting discharge of gastric chyme to the duodenum.

The interplay between hydrogen ions, bicarbonate ions and osmolality in the anterior duodenum modulating gastric function in the conscious calf.

1. Gastric emptying, gastric acid and pepsinogen secretion were assessed simultaneously in the conscious calf using the test meal and duodenal perfusion technique (Bell & Mostaghni, 1975).2. Duodenal infusion of NaCl at a constant osmolality of 300 m-osmole/kg, but with pH ranging from 2.0 to 12.0, did not alter the high level of gastric emptying and secretion already reported for isotonic NaCl or NaHCO(3) alone (Bell & Mostaghni, 1975; Bell & Webber, 1979). Gastric function, therefore, is either unaffected by gastric chyme at pH 2.0-12.0 entering the duodenum, or else isotonicity is dominant over pH in activating duodenal receptors which increase motor activity.3. When the pH of the isotonic NaCl was reduced by the addition of HCl to below pH 2.0, inhibition of gastric function occurred in direct proportion to the amount of titratable acid present in the infusate. The H(+) moiety of isotonic duodenal infusates of pH < 2.0 dominates activation of osmoreceptors and so inhibits motor activity.4. When the same amount of acid but at differing concentrations and infusion rates was introduced into the duodenum uniform inhibition of gastric function occurred. This result indicates that duodenal acid receptors respond to acid concentration and flow rate to produce an integrated response in proportion to the amount (concentration x volume) of acid present.5. Isotonic NaHCO(3) solutions adjusted to pH 8.1-12.0 by the addition of NaOH, like isotonic NaCl infusions, did not affect gastric function until pH 11.0-12.0, when significant inhibition occurred. This inhibitory effect of isotonic NaHCO(3) at high pH is probably due to CO(3) (2-), since Na(2)CO(3) and Li(2)CO(3), but not LiCl, produce a similar inhibitory effect on gastric function.6. The inhibitory effect of carbonate gives some support to the existence of a CO(2)-sensor as suggested by Hunt & Knox (1972), whereby increased P(CO2) produced by intracellular or intercellular neutralization of CO(3) (2-) by duodenal H(+) activates acid receptors. But other experiments reported here, where simultaneous perfusion of HCl and excess NaHCO(3) produced a rise in intraluminal P(CO2), did not inhibit gastric function, which is contrary to the idea of a direct intraluminal effect of CO(2) on duodenal receptors.7. The pH, P(O2), P(CO2), HCO(3) (-) and base excess of venous blood showed no detectable change during duodenal infusion of either acidic or alkaline solutions. Metabolic acidosis or alkalosis, therefore, cannot be considered to play any part in controlling gastric function. The results thus corroborate the notion that the receptors controlling gastric function are localized in the intestinal mucosa.8. Our results suggest that interplay between acid and osmolality of gastric chyme occurs in the rostral part of the duodenum to produce a graded inhibitory effect which by negative feedback modulates the gastric effectors that normally activate smooth muscle, parietal cells and zymogen cells.

The effect on salt appetite and the renin-aldosterone system on replacing the depleted ions to sodium-deficient cattle.

1. Sodium depletion which occurred in cattle following exteriorization of a parotid duct produced depression of both plasma and salivary sodium, acidosis, elevated plasma aldosterone and renin activity. Increased sodium appetite, characteristic of sodium depletion, was assessed by operant behaviour where scoring of panel pressing for NaHCO(3) rewards showed change in sodium appetite.2. Sodium-depleted calves readily drank the calculated ionic deficit as a hypertonic solution (4 l.) in a few minutes, or as an isotonic solution (16 l.) usually within 30 min.3. When the ionic deficit was restored by either i.v. infusion or drinking, sodium appetite was reduced significantly. The suppression of sodium appetite was more rapid when the depleted ions were replaced by drinking (30 min) than by i.v. infusion (2 hr) but in both circumstances the effect was short lived since sodium appetite redeveloped within 3 hr.4. The rapid return of sodium appetite following restoration of the ionic deficit occurred even when the plasma sodium level was normal. Other biochemical changes resulting from sodium depletion, such as acidosis and reduced salivary sodium, could not be correlated with variation in sodium appetite.5. Rapid infusion of Ringer saline (4 l.) did not inhibit the sodium appetite, which suggests that neither vascular volume changes per se nor vascular baroreceptors control sodium appetite in sodium-deficient calves.Plasma aldosterone fell rapidly following infusion of the hypertonic solution but only slightly with the isotonic infusion. The change in plasma hormone level was not related to changes in sodium appetite.6. Drinking the hypertonic solution produced a marked reduction in panel pressing for NaHCO(3) with a rapid rise in plasma sodium. Consumption of the larger volume of isotonic solution also inhibited sodium intake but plasma sodium remained low. A secondary increase in plasma renin activity (p.r.a.) occurred following ingestion of the hypertonic solution, but both p.r.a. and aldosterone fell to normal levels over the next 6 hr when the cattle again showed marked sodium appetite. It is possible that these effects may be due to ion and fluid movement between gut and extracellular fluid and reflect osmolality changes or tissue dehydration.7. It is concluded that the sodium appetite of sodium deficient cattle is only temporarily alleviated by restoration of the depleted ionic loss, and that the behavioural response to seek sodium rewards is independent of plasma sodium, p.r.a., aldosterone and volume changes in the gut and vascular system.8. Recent reports suggest that sodium appetite may be controlled by receptors in the hypothalamus or by angiotensin II in the brain. In cattle the capacious gut may also be involved, since sodium appetite is inhibited more rapidly when the depleted ions are taken orally than by i.v. infusion.

A comparison of duodenal osmolality and energy content as controlling factors of gastric emptying in the calf.

1. The relative importance of energy content and osmolality of the duodenal chyme in the feed-back control of gastric emptying was investigated in the milk-fed calf fitted with gastric (abomasal) and duodenal re-entrant cannulae. 2. Duodenal infusion of isosmolal solutions, containing glucose, fructose or galactose, with a range of combustible energy content (0--1.46 MJ/l.) resulted in the same high rate of emptying of test meals from the stomach (abomasum). Abomasal emptying was, therefore, not affected by the energy content of the duodenal infusate. 3. Gastric secretion of acid and pepsinogen, and the volume of gastric secretions produced were also unaffected by the energy content of isosomolal duodenal infusates. 4. The results of the study show that the combustible energy content of the intestinal chyme is not a direct determinant of gastric function and that total osmolality of the lumenal contents is the only parameter influencing duodenal receptors under the conditions of our experiments.

A study of olfaction and gustatory senses in sheep after olfactory bulbectomy.

The importance of taste and smell in discrimination of sodium salts was examined in normal and anosmic sheep. To test for anosmia, faeces of pig, calf and sheep were used as noxious odours. Intact sheep, and sheep with one olfactory bulb removed avoided the aversive stimulus whereas following total bulbectomy, the faecal odour was no longer a deterrent. Olfactory bulbectomy did not affect food intake but changes in fluid intake, urinary loss and electrolyte excretion were apparent. In two-choice preference tests, normal sheep showed a marked aversion for 0.48 M NaHCO3 and 0.51 M NaCl when compared to water. Following either unilateral or bilateral olfactory bulbectomy the aversion for sodium salts persisted but was less extreme. This suggests that in the final discrimination of sodium salts the sense of taste is dominant but olfaction or the olfactory bulb may have a minor role.