Biomedical subjects

R S Weisinger

Publications and source records attributed to R S Weisinger.

At least 37 records · Page 2Linked to original sources

PubMed1999

Water drinking in rats resulting from intravenous relaxin and its modification by other dipsogenic factors.

The purpose of the study was to determine whether iv infusion of relaxin would acutely stimulate water drinking in rats and, if it did, whether such drinking is affected by other dipsogenic stimuli or is blocked by centrally administered losartan. iv infusions of human gene 2 relaxin at doses of 25, 40, 55, or 80 microg/kg x h for 1 h induced dose-dependent water drinking in both male and female rats within 15-30 min of commencement of infusions. iv infusion of a nondipsogenic dose of angiotensin II (0.5 microg/h), combined with relaxin (40 microg/kg x h), almost tripled the relaxin-induced water intake. iv infusion of hypertonic (1 M) NaCl did not potentiate relaxin-induced drinking. Intracerebroventricular injection of the angiotensin AT1 antagonist losartan (10 microg) reduced water drinking induced by iv infusion of relaxin. The water drinking induced by iv infusion of relaxin in the rat suggests that blood-borne relaxin may be a dipsogenic hormone. Potentiation of this relaxin-induced drinking by moderate levels of circulating angiotensin II is additional evidence in support of this view. The results also indicate that a central angiotensinergic neural pathway, utilizing AT1 receptors, subserves relaxin-induced drinking.

Angiotensin II↗

PubMed1998

Evidence that brain angiotensin II is involved in both thirst and sodium appetite in baboons.

The roles of ANG II in the brain mechanisms subserving thirst and Na appetite in baboons were investigated by chronic intracerebroventricular infusions of ANG II and AT1-receptor antagonists using subcutaneous miniosmotic pumps and by oral administration of captopril. ANG II at 3 or 5 micrograms/h for 7 days increased water intake from 2,455 +/- 107 to 7,052 +/- 562 ml/day by day 6 and 300 mM NaCl intake from 8.3 +/- 1.1 to 275 +/- 87 mmol/day by day 5. Concurrent intracerebroventricular losartan (300 micrograms/h) did not substantially reduce these responses, but they were abolished by intracerebroventricular ZD-7155 (50 micrograms/h). The increase of 300 mM NaCl intake when it was offered after intramuscular injection of furosemide, 2 mg . kg-1 . day-1 for 3 days, was unaltered by intracerebroventricular losartan (300 micrograms/h) but was reduced by intracerebroventricular ZD-7155 (50 micrograms/h) infused throughout Na depletion/repletion; oral captopril (1 g, 3 and 18 h before access to 300 mM NaCl) also reduced NaCl intake. Restriction of water intake to 25% of daily intake for 3 days caused a high intake of water on day 4, and this was reduced by intracerebroventricular losartan (300 micrograms/h) infused throughout the period of water restriction/rehydration. These novel results in a primate species suggest that brain ANG II is involved in both thirst and Na appetite, acting via AT1 receptors.

Administration, Oral↗

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

Distribution of Fos immunoreactivity in the lamina terminalis and hypothalamus induced by centrally administered relaxin in conscious rats.

The effect of intracerebroventricular (ICV) injections of synthetic human or rat relaxin (25 or 250 ng) on the distribution of Fos detected immunohistochemically in the rat forebrain was investigated. Following ICV relaxin, many Fos-positive neurons were observed in the periphery of the subfornical organ, dorsal part of the organum vasculosum of the lamina terminalis, throughout the median preoptic nucleus, supraoptic nucleus and hypothalamic paraventricular nucleus. Such effects did not occur following ICV injection of artificial cerebrospinal fluid or the separated A and B chains of relaxin, nor following the intravenous injection of 250 ng of relaxin. Both vasopressin and oxytocin containing neurons identified immunohistochemically in the supraoptic and paraventricular nuclei exhibited Fos following ICV relaxin, and many neurons in the medial parvocellular part of the paraventricular nucleus contained Fos. The results indicate that centrally administered relaxin may increase neuronal activity in regions of the hypothalamus and lamina terminalis which are associated with cardiovascular and body fluid regulation and oxytocin secretion.

Animals↗

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↗

PubMed1996

Physiological actions of angiotensin II mediated by AT1 and AT2 receptors in the brain.

1. Autoradiographic binding studies have shown that the AT1 receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT1 receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord. 2. While there are differences between species, AT2 receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat. 3. Circulating AngII acts on AT1 receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking. 4. Centrally administered AngII may act on AT1 receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion. 5. Recent evidence shows that centrally administered AT1 antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that n angiotensinergic neural pathway has a role in osmoregulatory responses. 6. Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT1 receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

Angiotensin II↗

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

Converting enzyme inhibition in rabbits: effects on sodium and water intake/excretion and blood pressure.

Earlier studies in rabbits revealed that in this species, in contrast to most other species studied, water intake was not influenced by injection or infusion of angiotensin II (ANG II). In order to establish whether ANG II has any role in the regulation of water intake of rabbits, a comprehensive study of the effect of converting enzyme inhibition was undertaken. Enalaprilat was given systemically in various doses to sodium- and water-replete, sodium-deplete, and water-deprived rabbits, and the intake and excretion of water and sodium was measured. In replete rabbits systemic injection of enalaprilat, 8 mg/kg and 8 micrograms/kg, but not 0.8 mg/kg, was followed by increased daily water intake. In sodium-deplete rabbits injection of enalaprilat, 80 mg/kg, was followed by water drinking within 1 h, and daily sodium intake was reduced. Systemic administration of ANG II increased, but did not restore to control level the sodium appetite of sodium-deplete rabbits attenuated by 80 mg/kg enalaprilat. Rabbits deprived of water for 24 h, however, drank the same amount of water after injection of vehicle or enalaprilat, 80 and 8 mg/kg. The efficacy of converting enzyme inhibition was also tested by measuring the blood pressure response to ANG I. Blood pressure responses revealed that in replete animals converting enzyme activity was depressed below control levels for 30 h after injection of 80 mg/kg enalaprilat. In sodium-deplete rabbits blood pressure fell following injection of 80 mg/kg enalaprilat and did not return to control level until 48 h after the injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗