Selenium deficiency in cattle associated with Heinz bodies and anemia.

Cattle grazing St. Augustine grass growing on peaty muck soils in the Florida Everglades developed anemia associated with the presence of Heinz bodies and suboptimal concentrations of selenium in blood. Selenium supplementation corrected the anemia, prevented Heinz body formation, increased the body weight of cows and calves, and elevated blood selenium. This may be the first recorded example of widespread anemia in a population due to selenium deficiency.

Endocrine and ingestive behavioral responses to fluid deprivation in sheep chronically exposed to ethanol.

Endocrine responses to fluid deprivation/restoration and preference for ethanol solution vs. water were assessed in sheep maintained for 5 months on a 10% ethanol solution as their sole source of fluid. Blood pressure, body weight, plasma composition and hormone levels of the alcohol maintained sheep were all within a normal range, except for high plasma concentrations of ANG II and ALDO. During fluid deprivation, AVP concentration increased and fluid-deprived sheep displayed a natriuresis and then a rehydration anti-natriuresis. Sheep did not drink the 10% ethanol solution avidly upon fluid restoration, preferring to drink steadily over the following 24 h; there was an associated increase in blood alcohol concentration (BAC). PRC, ANG II and ALDO all increased throughout the fluid restoration period, whereas plasma AVP and ANP gradually fell. In a separate experiment when water was also supplied to the sheep, they preferred water to 10% ethanol; however, alcohol intake was not eliminated. Overall, this degree of chronic consumption of 10% ethanol solution did not appear to adversely affect physiological mechanisms concerned with body fluid homeostasis after fluid deprivation conditions.

Cardiovascular effects of long-term central and peripheral administration of urocortin, corticotropin-releasing factor, and adrenocorticotropin in sheep.

The neuroendocrine hormones ACTH and corticotropin- releasing factor (CRF), which are involved in the stress response, have acute effects on arterial pressure. New evidence indicates that urocortin (UCN), the putative agonist for the CRF type 2 receptor, has selective cardiovascular actions. The responses to long-term infusions of these hormones, both peripherally and centrally, in conscious animals have not been studied. Knowledge of the long-term effects is important because they may differ considerably from their acute actions, and stress is frequently a chronic stimulus. The present experiments investigated the cardiovascular effects of CRF, UCN, and ACTH in conscious sheep. Infusions were made either into the lateral cerebral ventricles (i.c.v.) or i.v. over 4 d at 5 microg/h. UCN infused i.c.v. or i.v. caused a prolonged increase in heart rate (HR) (P < 0.01) and a small increase in mean arterial pressure (MAP) (P < 0.05). CRF infused i.c.v. or i.v. progressively increased MAP (P < 0.05) but had no effect on HR. Central administration of ACTH had no effect, whereas systemic infusion increased MAP and HR (P < 0.001). In conclusion, long-term administration of these three peptides associated with the stress response had prolonged, selective cardiovascular actions. The striking finding was the large and sustained increase in HR with i.c.v. and i.v. infusions of UCN. These responses are probably mediated by CRF type 2 receptors because they were not reproduced by infusions of CRF.

Evaluation of the biological properties of parathyroid hormone and analogues in a vascularly isolated parotid gland-based assay.

Infusion of bovine parathyroid hormone (bPTH) preparations into the arterial blood supply of the vascularly isolated parotid gland in anaesthetized sheep increases salivary phosphate concentration and gland blood flow rate with rapid onset and offset of action. These responses have been used as a bioassay for PTH and PTH analogues and for assessing the properties of an in-vitro inhibitory analogue [Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide. [Nle-8, Nle-18, Tyr-34]bPTH-(1-34)amide at 10(-9) to 10(-8) mol/l was four to five times more potent than bPTH(1-34) on both salivary phosphate and blood flow assays. Human PTH(1-34) was not significantly more potent than bPTH(1-34). The [Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide analogue had very slight agonist activity at 3 X 10(-7) mol/l and at a 100:1 ratio of analogue to PTH it completely inhibited the action of bPTH(1-34) on phosphate secretion and gland blood flow. It caused partial inhibition at 10:1 and had no evident effect at 1:1. These results differ from previous in-vitro results and indicate that the preparation may be valuable for evaluation of agonist and antagonist analogues of PTH. The vascularly isolated parotid gland of the sheep permits repeated random testing of analogues in a control-test-control sequence and the results indicate high sensitivity to PTH in a rapidly reactive in-vivo system with two responding parameters.

Local action of parathyroid hormone (1-34) and (1-84) at the parotid gland of sheep.

Administration of bovine parathyroid hormone (PTH) preparations increased the phosphate concentration in the parotid saliva of sheep. Data on the site of action of PTH (1-84) were obtained by (a) equimolar infusions of PTH (1-84) and (1-34) directly into the arterial blood supply of the vascularly isolated parotid gland in anaesthetized sheep, (b) intravenous infusion of PTH (1-84) at a similar rate and (c) intra-arterial infusion of PTH (1-84) with complete drainage of the venous effluent from the gland during the infusion. Results showed substantial time- and dose-response identity of the two peptides, at 10(-9) to 4 X 10(-9) mol/l in arterial blood, in raising salivary phosphate concentration. The effect of PTH (1-84) was not due to recirculated fragments because the response was obtained when recirculation was prevented by complete venous drainage and little or no response occurred when the same infusion was given i.v.

A dose-response comparison of the actions of angiotensin II and angiotensin III in sheep.

Comparisons of aldosterone responses to [des-Asp1]-angiotensin II and angiotensin II, often at single dose levels, have shown a wide range of potency ratios. Therefore four-point dose-response comparisons were performed in sodium-replete sheep, using i.v. infusion rates of angiotension II and angiotensin II amide that reproduced the physiological range of blood concentration of angiotensin II for sheep. Angiotensin III was infused i.v. at the same rates. Effects on arterial blood pressure, cortisol secretion rate, adrenal blood flow and plasma levels of NA+ and K+ were also compared. The potency ratio, angiotensin III : angiotensin II amide, was 0.87 for actual aldosterone secretion rate and 0.90 for the calculated increase in aldosterone secretion. For angiotensin III : angiotensin II the ratios were 0.80 and 0.91 respectively. These ratios were not significantly different from 1.00 but the tendency for angiotensin II to be slightly more potent was probably due to a contribution from derived angiotensin III during infusion of angiotensin II. Angiotensin II or angiotensin II amide was approximately four times as potent as angiotensin III in raising arterial blood pressure. Cortisol secretion rate was slightly but significantly increased by all peptides at the higher infusion rates. Infusions had no effect on adrenal blood flow or plasma levels of Na+ but raised plasma levels of K+ slightly. These results confirm the conclusion from adrenal arterial infusion experiments that angiotensin II and III are almost equipotent in stimulating aldosterone secretion in sheep.

Plasma renin activity and blood corticosteroids in the Australian lungfish Neoceratodus forsteri.

Plasma renin activity (PRA) and blood aldosterone and deoxycorticosterone levels were measured in Australian lungfish. Plasma renin activity was depressed after intravenous infusions of iso-osmotic (0-6%) NaCl but not after hypo-osmotic (0-3%) infusions. The presence of PRA in this fish is consistent with prior reports of renal renin activity in other sarcopterygian fishes. The results of the infusion experiments suggest that a fall in plasma osmolality or electrolyte concentrations may oppose the reduction in renin release in response to volume expansion. Aldosterone and deoxycorticosterone were identified in the blood of Neoceratodus. The concentrations of both appeared higher in females than in males. Infusions of [5-valine]-angiotensin II amide for 2-4 h at rates known to increase blood pressure in this species did not alter blood aldosterone concentrations. This negative finding may suggest that the renin/angiotensin system is not involved in aldosterone regulation in Neoceratodus or that angiotensin receptors involved in regulation of steroidogenesis have a greater specificity for endogenous angiotensin than do vascular receptors.

Role of brain angiotensin in thirst and sodium appetite of rats.

The role of brain angiotensin II (ANG II) in water, Na and food intake of rats was studied. Intracerebroventricular (i.c.v.) infusion (100 micrograms/h) of the non-peptide ANG II receptor antagonist losartan (type 1), but not PD123319 (type 2), completely blocked water intake caused by i.c.v. infusion of ANG II at 50 ng/h. Following food deprivation, food intake was reduced by PD123319 and associated water intake was decreased by losartan or PD123319. Neither water intake after water deprivation nor Na intake after Na depletion was altered by losartan or PD123319. In conclusion, evidence was consistent with a role for brain ANG II in both food and water intake after food deprivation but not in thirst subsequent to water deprivation or Na intake after Na depletion alone.

The role of angiotensin II in ingestive behaviour: a brief review of angiotensin II, thirst and Na appetite.

From the outset, the study of angiotensin II (Ang II) in body fluid homeostasis has been both complicated and intriguing. Since the publication of an early report of the dipsogenic action of this peptide, the pursuit of the role of Ang II in thirst and Na appetite has continued for the last 25 years. This pursuit captured the attention of all workers interested in the behavioural/physiological regulation of body fluid balance, with major contributions being made by James T. Fitzsimons and his colleagues. In spite of its powerful dipsogenic actions, delineation of its precise role in physiological thirst has been elusive and difficult to demonstrate. The influence of Ang II on Na intake took longer to show convincingly. However, in contrast to thirst, the role of Ang II in physiological Na appetite has been demonstrated clearly. The technological advances made during the recent years have greatly increased our ability to delineate the neurobiological context of Ang II-mediated responses. Thus, the future is promising in regard to illuminating the subtleties of the role of Ang II in body fluid balance.

Central administration of atrial natriuretic peptide suppresses sodium and water intake of sheep.

The effect of intracerebroventricular (i.c.v.) infusion (20 micrograms/h) over 3 h) of human alpha-atrial natriuretic peptide (ANP) on Na and water intake of sheep was studied. I.c.v. infusion of ANP decreased (p less than 0.01) Na and water intakes of water-deprived sheep but did not affect significantly Na or water intakes of Na and water-replete sheep. In addition, i.c.v. infusion of ANP decreased (P less than 0.05) Na and water intakes of sheep infused i.c.v. with angiotensin II. The results suggest that ANP may act on brain mechanisms concerned with both Na appetite and thirst. These mechanisms may involve action on the angiotensin II component of sodium appetite but effects on other factors determinant of appetite cannot be excluded at present.

Opening the blood-brain barrier to zinc.

Sheep with guide tubes implanted over the brain lateral ventricles, in order to facilitate episodic sampling of cerebrospinal fluid (CSF), were used to determine the effects of increasing cranial blood osmolality or electroconvulsive shock (ECS) on the permeability of the blood-brain barrier (BBB) to zinc. Zinc acetate solution (1 mg Zn/ml) was infused intravenously (i.v.) at 1.0 ml/min for 30 min and then continuously at 0.125 ml/min. This infusion increased plasma total zinc concentration (pZn) approximately 10-fold without altering CSF zinc concentration (CSFZn). After 1.5-3.5 h, 4 M NaCl was infused at 5-10 ml/min for 10 min into one carotid artery with the other carotid artery occluded, or the animals were anaesthetized and given an ECS (140 V, 2 s). Paired samples of blood and CSF were collected before and after these treatments. Results were: (i) CSFZn was approximately one tenth of pZn; (ii) zinc administered i.v. was almost completely excluded from the CSF; (iii) increased cranial blood osmolality or ECS increased CSFZn in all experiments, but the time course and extent of the rise were variable. CSFZn reached the concentrations of zinc in normal sheep plasma in some experiments; (iv) CSFZn subsequently fell towards the low values of zinc in normal CSF; (v) the animals suffered no evident ill-effects from either procedure. The procedures may, therefore, be used for reversible opening of the BBB to particles such as zinc in conscious or anaesthetized sheep with no troublesome sequelae.

Central administration of somatostatin suppresses the stimulated sodium intake of sheep.

The effect of intracerebroventricular (i.c.v.) infusion (50 micrograms/h over 3 h) of somatostatin (SOM) on Na and water intake of sheep was determined. In Na-deplete sheep, infusion of SOM-(28) but not SOM-(14) decreased (P less than 0.05) Na intake, while both SOM-(28) and SOM-(14) increased water intake. I.c.v. infusion of SOM-(28) did not significantly affect Na or water intake of Na-replete sheep. I.c.v. infusion of SOM-(28) decreased (P less than 0.01) Na intake but did not alter the high water intakes of water-deprived sheep or sheep infused i.c.v. with angiotensin II. The results are compatible with an inhibitory action of somatostatin on stimulated brain mechanisms subserving Na appetite but not on stimulated brain mechanisms subserving thirst. Somatostatin may antagonize the inhibition of thirst in Na-deplete sheep. The results suggest that somatostatin may have a regulatory role in ingestive behavior concerned with body fluid and Na homeostasis. The difference between SOM-(14) and SOM-(28) in decreasing the Na intake of Na-deplete sheep may be due to a difference in potency or mechanism of action.

Effect of varying the composition of CSF on urinary excretion in the conscious rat.

The effect of 4 h intracerebroventricular (i.c.v.) infusion of various solutions on the renal excretion of Na and K and urinary flow rate was examined in conscious unrestrained rats not water-loaded. I.c.v. infusion of iso- or hypo-osmotic solutions with low [Na] induced a diuresis but did not alter renal excretion of Na or K. I.c.v. infusion of hyperosmotic solutions with normal or elevated [Na] induced a natriuresis and kaliuresis. Hyperosmotic mannitol solutions caused a diuresis but hyperosmotic NaCl or sucrose solutions caused a diuresis only when the rats drank water and/or sodium solution during the infusion period. I.c.v. infusion of hyperosmotic NaCl but not hyperosmotic mannitol increased blood pressure. The results are consistent with the involvement of cerebral osmosensors in the control of urinary excretion of Na and K, and of cerebral Na sensors in the control of urinary flow rate. Increased blood pressure, as occurred during i.c.v. infusion of hyperosmotic NaCl, may also contribute to the increased excretion of Na and K.

Thirst induced by increasing brain sodium concentration is mediated by brain angiotensin.

Thirst, the longing or compelling desire to drink, arises physiologically by two main mechanisms-extracellular and cellular dehydration. The hormone angiotensin II has been implicated in the former but not in the latter brain mechanism. To test this apparent difference, experiments in 5 mammalian species examined the effect of intracerebroventricular infusion of losartan, an angiotensin II type I receptor antagonist, on the third induced by intracerebroventricular infusion of an artificial cerebrospinal fluid made hypertonic by the inclusion of 500 mM NaCl. The losartan infusion reduced the water intake due to increased brain sodium concentration in all 5 species, cattle, sheep, rabbits, rats and mice. Thus, the thirst evoked by cellular dehydration, as well as the thirst evoked by extracellular dehydration, may be mediated by angiotensin II.

Na depletion-induced Na appetite of sheep is independent of brain angiotensin II.

Previous experiments indicated that the Na appetite of Na-deplete sheep is decreased by systemically administered captopril. The assumption that captopril does not readily cross the blood-brain barrier, lead to the conclusion that circulating ANG II acting in brain areas without a blood-brain barrier, i.e., circumventricular organs such as the subfornical organ or organum vasculosum of the lamina terminalis, contributes to Na appetite induced by Na depletion. The present experiments investigated the possibility that systemically administered captopril does, in fact, cross the blood-brain-barrier and thereby influence brain angiotensin II formation and that brain angiotensin II contributes to Na depletion-induced Na appetite of sheep. The results showed that systemically administered captopril blocked water intake caused by intracerebroventricular infusion of angiotensin I, and that Na depletion induced Na appetite was not decreased by intracerebroventricular infusion of various antagonists of the renin-angiotensin system. Thus, the results suggest that although captopril crosses the blood-brain-barrier and can influence the formation of brain angiotensin II, brain angiotensin II is not involved in the Na appetite of Na-deplete sheep.

Sodium intake and reproduction in BALB/C mice.

The effect of sodium intake on the reproductive performance of BALB/C mice was assessed in four groups of 11 or 12 mice that received ad lib access to low or higher sodium food (LSF 4-5, HSF 120-143 mmol Na+/kg). The two groups that received HSF had (mean values) 100% matings, 83 and 91% litters, 5.9 pups/litter, pups weighing 2.05 and 2.22 g (3 days after birth) and 10.47 and 10.96 g at weaning (19 days). One of the HSF groups that also had 300 mM NaCl to drink did not show any benefit. Two groups received LSF, and one of them also received 30 mM NaCl. The group given LSF only had 83% matings, 20% litters, 1.5 pups/litter, and pups that were significantly smaller at birth and at weaning. However, the LSF group given 30 mM NaCl to drink performed almost as well as the two HSF groups. The results show that (a) the daily sodium requirement for optimal reproduction was > or = 400 (micromol/day, based on voluntary sodium intake late in gestation and lactation; (b) sodium deficiency was the cause of reproductive deficiency in mice on LSF; (c) severe sodium deficiency suppressed reproduction primarily at the gestation step; (d) this deficiency could be prevented by the voluntary sodium intake of mothers with access to salt solution; and (e) pups on the LSF showed an avid innate salt appetite when offered salt solution at 12 days of age.

The effect of adrenocorticotrophic hormone on water intake in mice.

The systemic administration of adrenocorticotrophic hormone (ACTH) stimulates the intake of sodium chloride and water in many species. In mice the daily intake of water may reach half of the total body water content. To establish whether this very high water intake was primary or secondary to the sodium chloride intake, Synacthen was infused s.c. at 2.8 micrograms/day by Alzet miniosmotic pump to mice that did not have access to sodium chloride solution. On low-sodium food, the daily water intake increased from 2.99 +/- 0.08 ml (mean +/- SEM) to 9.85 +/- 0.74 ml (p < 0.05, n = 6) by day 7 of infusion and remained significantly higher than the control value until the fourth postinfusion day. On high-sodium food, the daily water intake also increased 350% from a higher baseline, 4.55 +/- 0.14 ml, and returned to the control value by the second postinfusion day. The same ACTH treatment for 4 days increased plasma [Na] and appeared to expand plasma volume. The results show that a high water intake caused by ACTH administration in mice is not secondary to a concurrent increase in sodium chloride intake. The water intake may be induced by stimulation of the secretion of adrenal steroid hormones which increase plasma [Na].

The dipsogen angiotensin II does not stimulate ethanol intake in mice.

Mice that were habituated to drinking ethanol solution and mice that had drunk water only (naive mice) were given an ICV infusion of angiotensin II (Ang II) at 2.9 ng/h for 8 days to determine the effect of chronic ethanol intake on the ingestive response to this potent dipsogen. Ang II infusion in alcohol-naive mice increased daily water intake from 3.7 +/- 0.2 ml (mean +/- SE, n = 6) to 11.0 +/- 1.5 ml on day 4 (p < 0.001) and to 18.3 +/- 2.6 ml on day 8 (p < 0.001). In subsequent experiments, mice had access to 4% ethanol solution up to day 4 and then to water for 4 days during the Ang II infusion. Alcohol-naive mice did not increase daily fluid intake until the water was provided on day 5; intake increased to 17.5 +/- 2.3 ml on day 8 (p < 0.001, n = 7). Mice accustomed to drinking 4% ethanol (4.3 +/- 0.3 ml/day) also did not increase intake until the water was provided; intake reached 22.9 +/- 3.0 ml of water on day 8 (p < 0.001, n = 7). Mice accustomed to drinking 10% ethanol behaved similarly (n = 4). Thus, alcohol-naive or -habituated mice did not respond to this dipsogenic stimulus until water was available; the thirst for water was unimpaired. Preference-aversion tests showed that mice drank little or no 4% ethanol (or even 2% ethanol) when water was also available. Taste aversion, plus previous experience from ingestion of ethanol in habituated mice, may explain the rejection of ethanol to quench Ang II-induced thirst. Experimental results obtained using other aversive solutions, 3 mM quinine and 300 mM KCl, suggest that postingestional, metabolic effects of solutes may also contribute to such rejection.

Angiotensin II stimulates intake of ethanol in C57BL/6J mice.

The influence of intracerebroventricular (i.c.v.) infusion of angiotensin II on intake of water and ethanol solutions was determined in C57BL/6J mice. Compared to other mice, C57 mice do not show an aversion to ethanol solutions. With both water and ethanol solutions available, the C57 mice consumed 40-60% of their total daily fluid intake as ethanol solution when the concentration of ethanol solution offered was 4-14%. When given a choice between 0.3 M KCl and either 4 or 10% ethanol solution, the mice clearly preferred the ethanol solution. With water only available, i.c.v. infusion of angiotensin II increased intake from 3-5 mL/day (baseline) to 11-12 mL/ day (Day 4 of infusion). A similar increase in intake occurred in mice with access to a nonpreferred solution of 0.3 M KCl. In comparison, when only 4% ethanol solution was available, angiotensin II increased intake to 7-8 mL/day, and when only 10% ethanol solution was available, intake was transiently increased. The results demonstrated that thirst for water caused by i.c.v. infusion of angiotensin II in C57 mice is similar to that observed in BALB/C mice. Unlike BALB/C mice, however, i.c.v. infusion of angiotensin II stimulated intake of ethanol solution. The failure of angiotensin II to cause a large increase in 4% ethanol solution or a sustained increase in 10% ethanol solution intake does not seem to be caused by an aversion to the taste of ethanol solution, but most likely due to postingestional factors.

Changes in sodium appetite in cattle induced by changes in CSF sodium concentration and osmolality.

Alteration of the sodium concentration in the cerebrospinal fluid (CSF) of sheep induces reciprocal changes in sodium appetite. Similar studies have now been performed in cattle. Heifers were prepared with a unilateral parotid fistula and guide tubes were implanted in the skull for the introduction of probes into the lateral ventricles in order to sample CSF and infuse artificial CSF solutions. The cows were Na depleted by loss of saliva for 46 hr and then given free access for 2 hr to 300 mM NaCl/NaHCO3 solution. Artificial CSF infusions at 1.9 ml/hr were begun one hour before Na access. In control experiments, the cows drank 26.4 +/- 1.2 l of Na solution in 2 hr, 1.2 +/- 0.2 l of water in the preceding hour, and 0.3 +/- 0.1 l of water during Na access. Sham or standard isotonic CSF infusions did not alter these values. CSF [Na+] rose from approximately 142 to approximately 148 mmol/l, attributable to the effects of drinking the large volume of hypertonic Na solution. Infusion of 500 mM NaCl CSF increased CSF [Na+] and reduced Na intake and increased water intake. Infusion of 700 mM mannitol: 150 mM NaCl CSF reduced CSF [Na+] and increased both Na and water intake. Infusion of a mixture of these solutions had no effect on CSF [Na+] and increased water intake only. Infusion of 270 mM mannitol CSF reduced CSF [Na+] and slightly reduced Na intake. Standard isotonic CSF containing 0.5 or 2.0 micrograms/ml of angiotensin II increased water intake only.(ABSTRACT TRUNCATED AT 250 WORDS)