Biomedical subjects

D A Denton

Publications and source records attributed to D A Denton.

At least 37 records · Page 2Linked to original sources

PubMed1997

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.

Angiotensin II↗

PubMed1997

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.

Angiotensin II↗

PubMed1997

Central infusion of the AT1 receptor antagonist losartan inhibits thirst but not sodium appetite in cattle.

Experiments in cattle compared the effects of intracerebroventricular (i.c.v.) infusions of losartan and PD-123319 on water intake caused by water restriction, i.c.v. infusion of hypertonic NaCl, or i.c.v. infusion of angiotensin II (ANG II). The effects of these receptor antagonists on sodium intake caused by sodium depletion were also examined. Losartan infusion caused dose-dependent inhibition of the high water intake caused by the physiological stimulus of water restriction or by ANG II infusion but did not affect salt appetite. PD-123319 infused at equimolar or greater (in ANG II experiments) doses did not affect water intake or salt intake due to sodium depletion. The results of these i.c.v. infusion experiments confirm our earlier proposal that the physiological regulation of water intake in cattle may be mediated by ANG II acting centrally via AT1 receptors. The dose of losartan that inhibited thirst in cattle did not inhibit sodium appetite, nor did an equimolar dose of PD-123319.

Angiotensin II↗

PubMed1997

Role of brain angiotensin II in thirst and sodium appetite of sheep.

The contribution of brain angiotensin II (ANG II) to thirst and Na+ appetite of sheep was evaluated. Thirst was stimulated by water deprivation, intracarotid or intracerebroventricular infusion of ANG II, or intracarotid or intracerebroventricular infusion of hypertonic solution. Intracerebroventricular infusion, over 1-3 h, of the ANG II type 1 (AT1) receptor antagonist, losartan, decreased or abolished water intake caused by all of the stimuli tested. Intracerebroventricular infusion of ZD-7155, another AT1-receptor antagonist, blocked ANG II-induced water intake. Neither losartan nor ZD-7155 infused intracerebroventricularly altered the Na+ appetite of Na(+)-depleted sheep. Intracerebroventricular infusion of losartan over 3 h, however, did block the increase in water intake and the decrease in Na+ intake caused by intracerebroventricular infusion of hypertonic NaCl in Na(+)-depleted sheep. Intracerebroventricular infusion of the ANG II type 2 (AT2) receptor antagonist, PD-123319, over 1-3 h, did not alter ANG II-induced water intake or Na+ depletion-induced Na+ intake. These results are consistent with the proposition that brain ANG II, working via AT1 receptors, is involved in the neural system controlling some aspects of physiological thirst and Na+ appetite. A role for AT2 receptors in physiological thirst or Na+ appetite is not supported by the present results.

Analysis of Variance↗

PubMed1996

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.

Angiotensin II↗

PubMed1996

Hypothalamic integration of body fluid regulation.

The progression of animal life from the paleozoic ocean to rivers and diverse econiches on the planet's surface, as well as the subsequent reinvasion of the ocean, involved many different stresses on ionic pattern, osmotic pressure, and volume of the extracellular fluid bathing body cells. The relatively constant ionic pattern of vertebrates reflects a genetic "set" of many regulatory mechanisms--particularly renal regulation. Renal regulation of ionic pattern when loss of fluid from the body is disproportionate relative to the extracellular fluid composition (e.g., gastric juice with vomiting and pancreatic secretion with diarrhea) makes manifest that a mechanism to produce a biologically relatively inactive extracellular anion HCO3- exists, whereas no comparable mechanism to produce a biologically inactive cation has evolved. Life in the ocean, which has three times the sodium concentration of extracellular fluid, involves quite different osmoregulatory stress to that in freshwater. Terrestrial life involves risk of desiccation and, in large areas of the planet, salt deficiency. Mechanisms integrated in the hypothalamus (the evolutionary ancient midbrain) control water retention and facilitate excretion of sodium, and also control the secretion of renin by the kidney. Over and above the multifactorial processes of excretion, hypothalamic sensors reacting to sodium concentration, as well as circumventricular organs sensors reacting to osmotic pressure and angiotensin II, subserve genesis of sodium hunger and thirst. These behaviors spectacularly augment the adaptive capacities of animals. Instinct (genotypic memory) and learning (phenotypic memory) are melded to give specific behavior apt to the metabolic status of the animal. The sensations, compelling emotions, and intentions generated by these vegetative systems focus the issue of the phylogenetic emergence of consciousness and whether primal awareness initially came from the interoreceptors and vegetative systems rather than the distance receptors.

Animals↗

PubMed1996

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].

Adrenocorticotropic Hormone↗

PubMed1996

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.

Alcohol Drinking↗

PubMed1995

Central action of basic fibroblast growth factor on ingestive behaviour in mice.

Intracerebroventricular (ICV) infusion of basic fibroblast growth factor (FGF-2) at 50 ng/h for 5 days in male BALB/c mice suppressed the daily intakes of water and food (n = 4). Intakes were reduced on the second day, and were suppressed until the second day after stopping the infusion. The same infusion for 4 days had little effect on the high intakes of 0.3 M NaCl solution and water induced by prolonged ICV infusion of angiotensin II, or the daily food intake in these experiments (n = 7). However, the same infusion for 3-4 days reduced the increased intake of NaCl solution in Na-depleted mice (n = 8), reduced the increased water intake of water-restricted mice (n = 6 or n = 7), and reduced daily food intake in both experiments. Ventricular enlargement was noted in mice at the end of these experiments but, for reasons advanced, did not appear to account for the responses. The results indicate that FGF-2 may have an inhibitory role in these ingestive behaviours.

Angiotensin II↗

PubMed1995

Influence of adrenal steroid hormones on sodium appetite of Balb/c mice.

The effects of adrenal steroid hormones on sodium appetite were determined in female Balb/c mice by the subcutaneous implantation for 7 days of slow-release pellets containing aldosterone, corticosterone, deoxycorticosterone (DOC) or 11-deoxycortisol, separately or in a "cocktail" combination. Placebo pellets were also implanted. The daily intake of 0.3 M NaCl was increased for 2 days by aldosterone (calculated 2.9 micrograms/day released) or corticosterone (240 micrograms/day) and for 7 days by DOC (4.8 micrograms/day). The combination of these steroids plus 11-deoxycortisol (95 micrograms/day) increased daily sodium intake nine-fold (days 3-7) and also increased water intake 1.5-fold. Placebo pellets had small effects on water intake on three days. Subcutaneous infusion of ACTH (Synacthen) at 2.8 micrograms/day for 7 days by mini-osmotic pump increased sodium intake five-fold and water intake three- or four-fold. Thus, several adrenal steroids evoked sodium appetite in Balb/c mice, DOC being the most potent at the doses used. The effects of individual steroids are consistent with their contribution to the effect of ACTH on sodium appetite.

Adrenal Cortex Hormones↗

PubMed1995

Behavior of sheep drinking ethanol solution.

Sheep that were habituated to drinking 10% (vol/vol) ethanol solution instead of water were subjected to proven thirst stimuli to study the effect of chronic ethanol intake on brain mechanisms subserving thirst. Sheep that had not previously drunk 10% ethanol were also tested. All sheep were trained to press a pedal that delivered 50 ml/press of fluid (either 10% ethanol or water) into a drinking cup. In some experiments, fluids were presented in bins. All animals had access to only one fluid at a time. Five ethanol-drinking sheep appeared healthy and maintained body weight over 18 mo. They always preferred water to 10% ethanol. The intracerebroventricular (icv) infusion of angiotensin II (ANG II) at 3.8 micrograms/h for 2 h increased ethanol intake from 15 +/- 10 to 200 +/- 55 ml in the 1st h, but 2,850 +/- 320 ml of water was drunk in the 2nd h. The icv infusion of 500 mM NaCl had a similar effect. After fluid deprivation for 22 or 46 h, ethanol intake in 1 h of access was only 280 +/- 40 and 400 +/- 90 ml, respectively, and 24-h intake was not increased. Water-drinking sheep drank 1,300 +/- 195 ml of water in 1 h after 22-h water deprivation, and 24-h intake was 1.5 times normal. The icv infusion of ANG II in these sheep increased water intake in 1 h from 10 +/- 10 to 1,630 +/- 250 ml and intake of 10% ethanol to only 310 +/- 60 ml. In conclusion, sheep accept 10% ethanol as a substitute for water for daily drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

PubMed1994

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.

Angiotensin II↗

PubMed1993

Forebrain lesions that disrupt water homeostasis do not eliminate the sodium appetite of sodium deficiency in sheep.

Brain structures located within the anterior wall of the third brain ventricle (subfornical organ, median preoptic nucleus and organum vasculosum of the lamina terminalis) are known to be involved in thirst as well as other aspects of body fluid and electrolyte balance. The present studies evaluated the role of these structures in the Na appetite of mildly or moderately Na-depleted sheep (sheep with a parotid fistula deprived of Na solution for 22 or 46 h). In addition, the role of these structures was tested in mildly Na-depleted sheep in which the Na appetite was enhanced by decreasing cerebrospinal fluid and brain extracellular fluid Na concentration (i.e., i.c.v. infusion of hypertonic saccharide solution) or was decreased by systemic infusion of hypertonic saline. The results indicated that sheep with lesions which reduced or eliminated daily water intake or water intake in response to hypertonicity of body fluids had, in all situations tested, appropriate changes in Na appetite (i.e., similar to their prelesion changes). Thus, the present experiments demonstrated that the brain areas involved in thirst as well as other aspects of body fluid and electrolyte balance are anatomically different from those involved in regulating Na appetite.

Animals↗

PubMed1993

Effects of cortisol on blood pressure and salt preference in normal humans.

1. Adrenocorticotrophic hormone (ACTH) and corticosteroids stimulate salt appetite in laboratory animals. The hypothesis tested was that cortisol administration increases salt preference in humans. 2. Sodium taste studies (detection and recognition thresholds, taste intensity and preference tests) were conducted before, during and after cortisol administration (200 mg/day for 5 days) in normal men on a free diet. 3. Cortisol significantly increased systolic blood pressure (SBP), 113 +/- 3 - 130 +/- 4 mmHg, P < 0.05; diastolic blood pressure (DBP), 65 +/- 3 - 81 +/- 2 mmHg, P < 0.05; mean arterial pressure (MAP), 81 +/- 2 - 97 +/- 3 mmHg, P < 0.05; and bodyweight, 72.9 +/- 3.0 - 75.4 +/- 3.3 kg, P < 0.05. 4. Salt detection and recognition thresholds, taste intensity and preference for sodium chloride were unchanged following cortisol.

Adult↗

PubMed1993

Sodium appetite in response to sodium deficiency in baboons.

Naive male baboons exhibit little hedonic intake of 300 mM NaCl but develop a robust Na appetite with Na deficiency. With the first episode of Na deficiency, increased drinking of saline solution occurs in the first 1-3 days, but correction of deficit is slow over 5-6 days. Na intake and repair of deficit become more rapid with experience. After three episodes of Na deficiency, the baboons immediately drink Na solution when given access and repair the deficit over 1-2 days. These experimental data showing an innate Na appetite in primates are important in relation to behavior of gorillas and chimpanzees in the wild and anthropological records of behavior toward salt sources. They open an avenue for physiological analysis of cerebral mechanisms subserving Na appetite in primates and humans.

Animals↗

PubMed1992

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.

Angiotensin II↗

PubMed1992

Thirst and brain angiotensin in cattle.

Cows that were normally hydrated or deprived of water were given intravenous or intracerebroventricular (icv) infusions of angiotensin I converting-enzyme inhibitors (CEI) or angiotensin II antagonists. Normally hydrated Na-deficient cows increased water intake in a dose-related manner in response to icv infusion of angiotensin I (n = 5). The response to 3 micrograms/h angiotensin I was abolished by concurrent icv infusion of the CEI captopril at 3 mg/h but not by intravenous infusion of captopril at 120 mg/h, which reduced Na appetite (n = 5). The icv infusion of captopril at 12 mg/h did not reduce the water intake of cows that were water restricted for 26.5 h (n = 4) or water restricted and Na deficient (n = 4). The icv infusion of the more lipophilic CEI ramipril at 3 mg/h (n = 7) did not reduce the water intake of normally hydrated or dehydrated cows but reduced the "need-free" intake of Na solution by dehydrated cows. The icv infusion of the nonpeptide antagonist Du Pont 753 at 3 mg/h (n = 7) reduced water intake in dehydrated cows. The results indicate that brain angiotensin may be involved in thirst in cattle. The data suggest that this brain angiotensin II may be formed by a pathway that does not include converting enzyme and that is sited inside the blood brain barrier, possibly in the median preoptic nucleus.

Angiotensin I↗

PubMed1992

Behavioral and tissue responses to severe phosphorus depletion in cattle.

Two-year-old Aberdeen Angus heifers were depleted of phosphorus (P) by loss of phosphate in saliva from a parotid gland fistula combined with a low-P diet. The inorganic phosphate concentrations (Pi) of plasma, parotid saliva, ruminal fluid, and feces were reduced, but cerebrospinal fluid Pi was unaltered. Plasma Pi fell to less than 1.0 mM in 12 wk, and the cows displayed an avid appetite for old bones. P-deficient cows preferred old weathered bones to fresh bones until the latter had aged for approximately 1.5 yr. They did not eat blood, peritoneal fat, or meat, fresh or aged for 2-3 yr. They did not eat Na or Ca phosphate salts or bone heated to greater than 250 degrees C. P-replete cows did not take or eat bones. The behavioral effects of P deficiency were associated with failure to gain body weight and maintain condition, significant bone changes indicated by reduced bone weight and specific gravity, osteopenia indicated by radiology, evidence of reduced bone formation indicated by plasma osteocalcin levels and histology, and abnormal estrous cycles. Prolonged P deficiency was associated with increased plasma concentrations of total Ca and 1,25-dihydroxyvitamin D and reduced plasma concentrations of parathyroid hormone.

Animals↗