Biomedical subjects

R S Weisinger

Publications and source records attributed to R S Weisinger.

At least 73 records · Page 4Linked to original sources

PubMed1989

Voluntary ethanol intake of individually- or pair-housed rats: effect of ACTH or dexamethasone treatment.

The effect of ACTH or dexamethasone treatment on ingestion of 10% ethanol, 0.5 M NaCl and water was studied in individually- and pair-housed rats. Crowding or decreasing the amount of space per rat by increasing the number of rats per cage from 1 to 2, together with the associated increase in social interactions caused a large increase in ethanol intake. In pair-housed rats and in rats housed alone, ACTH treatment caused a large increase in Na intake but no change in ethanol intake. In pair-housed rats and in rats housed alone, dexamethasone treatment caused no change in either ethanol or Na intake. Thus, it would appear that the induction or maintenance of a high ethanol intake of rats during crowding, a presumed social stressor, can not be attributed entirely to either an increase in blood ACTH levels with the subsequent increase in glucocorticoid hormones or to a decrease in blood ACTH and natural glucocorticoid hormone levels. However, the possibility that ACTH and/or adrenocorticoid hormones, combined with other physiological or environmental factors, causes stressor-induced ethanol intake cannot be excluded.

Adrenocorticotropic Hormone↗

PubMed1989

Sodium appetite and thirst in cattle subjected to dehydration.

Cows having free access to water (hydrated) or deprived of water for 26.5 h (dehydrated) were infused for 3 h with angiotensin II or captopril solutions intravenously (iv) or intracerebroventricularly (icv) beginning 1 h before access to 0.3 M NaHCO3/NaCl solution for 2 h. The results agree with the results of the experiments with the same agents and doses in Na-deficient cows. Only iv infusion of angiotensin II stimulated Na appetite and only icv infusion of angiotensin II stimulated thirst. Therefore, barriers to the penetration of angiotensin II in the brain determined the particular site of action and elicited response. Dehydration did not stimulate Na appetite and, as shown previously, Na deficiency did not stimulate thirst, but both behaviors seem to be influenced by angiotensin-related mechanisms in the brain. The inability of iv angiotensin II to stimulate Na appetite in hydrated cows might be explained by the lack of a response caused by, and common to, Na deficiency and dehydration, e.g., upregulation of angiotensin II receptors, or reduced extracellular fluid volume.

Animals↗

PubMed1988

Feeding and drinking behaviour following angiotensin converting enzyme blockade: role of injectant pH.

Angiotensin converting enzyme (ACE) is a circulating dipeptidase which has a broad specificity and is known to metabolise a range of circulating peptides. While a number of circulating peptides are believed to modulate food intake, it is not known if ACE plays a role in the control of feeding behaviour and therefore in this study we have examined the effect of the potent, specific ACE antagonists captopril (SQ 14225) and enalapril (MK421) on food and water intake following food deprivation and 2-deoxyglucose treatment in the rat. One hour captopril (50 mg/kg, IP) pretreatment significantly reduced the food intake of 24 hr food deprived rats. Because captopril solutions have a low pH (2.0), the effect of buffered captopril on food intake following 24 hr food deprivation was also examined. Buffered captopril also significantly reduced the food intake of 24 hr food deprived rats, but not to the same extent as unbuffered captopril. Naloxone pretreatment (1 mg/kg, IP) did not antagonize the effect of captopril on food intake indicating that the anorexic action of captopril was not due to alterations in opiate peptide levels. Buffered captopril did not reduce the food intake of food-replete rats receiving 2-deoxyglucose (300 mg/kg, IP) or alter blood gases or pH. However, an equimolar buffered dose of the structurally different ACE inhibitor enalapril failed to significantly alter food deprivation-induced food intake, suggesting that this action of captopril in reducing food intake was unrelated to ACE blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1988

Atrial natriuretic peptide inhibits water and sodium intake in rabbits.

The effect of atrial natriuretic peptide (ANP) on water and sodium intake was investigated in wild rabbits, a species which does not drink water following i.c.v. or i.v. administration of angiotensin II but develops sodium appetite following i.c.v. infusion of angiotensin II. ANP was given during or after depletion of extracellular fluid volume: hemorrhage, fluid deprivation and administration of furosemide. Systemically administered ANP reduced the water, but not the sodium intake of wild rabbits. I.c.v. administration of ANP inhibited both water and sodium intake. The suppression of thirst following both i.v. and i.c.v. administration of ANP indicates that inhibition of the effect of angiotensin II is not the exclusive mechanism and the circumventricular organs are probably not the exclusive sites of action for ANP. The inhibition of sodium appetite in wild rabbits was consistent with earlier proposals that ANP acts through the inhibition of the effects of angiotensin II. Reduction of food intake coincident with administration of ANP was also noted, but dose-dependent decrease was not observed.

Angiotensin II↗

PubMed1988

The effect of captopril or enalaprilic acid on the Na appetite of Na-deplete rats.

1. The converting enzyme inhibitors, captopril (SQ14 225, Squibb) or enalaprilic acid (MK 422, Merck Sharp and Dohme), were used to evaluate the role of angiotensin II in sodium (Na) appetite of Na-deplete rats given a choice of water and 0.5 mol/l NaCl to drink. Also, the effect of these drugs on taste was evaluated in water-deprived Na-replete rats and in Na-deplete rats given a choice of NaCl, sucrose and water. 2. Intraperitoneal (i.p.) injection of furosemide (20 mg/kg) increased urinary Na loss by 1.3-1.4 mmol and subsequent Na intake by 1.5-1.8 mmol. This increase in Na intake was abolished by a high dose of captopril (50 mg/kg, i.p.) or enalaprilic acid (80 mg/kg, i.p.), but was enhanced by a low dose of captopril (50 micrograms/kg, i.p.). 3. There was no clear evidence that either captopril or enalapril affected taste for NaCl, sucrose or water in water-deprived Na-replete rats. However, the high dose of captopril or enalapril decreased the intake of NaCl and sucrose in Na-deplete rats. 4. Thus, while the results are consistent with the possibility that angiotensin II is involved in Na appetite induced by Na depletion and that the difference between the high and low doses of converting enzyme inhibitors on Na appetite may be related to their relative effectiveness in blocking angiotensin I conversion at central sites, the observation that sucrose intake is decreased by high dose converting enzyme inhibitor in Na-deplete rats suggests that other actions of the converting enzyme inhibitors may be involved.

Angiotensin II↗

PubMed1988

Angiotensin-related sodium appetite and thirst in cattle.

Cows depleted of Na by loss of saliva from a parotid fistula for 46 h had an avid appetite for Na solution. They drank 21.0 +/- 1.6 liter of 0.3 M NaHCO3-NaCl solution during 2 h of access but little or no water during that time. Solutions of angiotensin II or captopril were infused for 3 h intravenously or into a lateral ventricle (intracerebroventricular) beginning 1 h before access to Na solution. Intravenous angiotensin II increased Na intake (to 26.8 +/- 2.9 liter, P less than 0.01) but did not alter water intake. Intracerebroventricular angiotensin II increased water intake but did not alter Na intake. Intravenous captopril reduced Na intake (to 11.0 +/- 2.1 liter, P less than 0.001) and concurrent intravenous angiotensin II prevented the reduction but concurrent intracerebroventricular angiotensin II did not. Intracerebroventricular captopril did not alter Na or water intake. Intravenous captopril reduced to zero the water intake during the hour before Na access, and concurrent intravenous angiotensin II prevented that reduction also. The dipsogenic action of intracerebroventricular angiotensin II was potentiated by intravenous captopril. The results of these experiments suggest that if angiotensin II receptors involved in the mechanism regulating Na appetite are in the brain, they are accessible only from the blood, e.g., in circumventricular organs. Thirst was inhibited by reduction of angiotensin II in blood but was stimulated only by angiotensin II acting inside the blood-brain barrier.

Angiotensin II↗

PubMed1987

Decrease of brain extracellular fluid [Na] and its interaction with other factors influencing sodium appetite in sheep.

It has been shown previously in sheep that physiological increase of cerebrospinal fluid (CSF) [Na] by infusion of 0.5 M NaCl artificial CSF causes a large reduction of sodium appetite of the sodium-deplete animal. Equivalent increase of CSF osmotic pressure caused by infusion 0.7 M mannitol artificial CSF which lowers CSF [Na] causes a doubling of sodium appetite. The results of the experiments here show that simple dilution of CSF [Na] with isotonic mannitol CSF, as distinct from use of hypertonic 0.7 M mannitol CSF, is an equally effective strong stimulus of sodium appetite. Lowering CSF [Na] concentration stimulates salt appetite in the severely sodium-deplete as well as in the mild to moderately sodium-deplete animal, and the effect of decrease of CSF [Na] on sodium appetite is sustained over 48 h. In addition, i.c.v. infusion of angiotensin II for the preceding 22 h at a rate which is an effective stimulus of both water and sodium solution intake in the sodium-replete animal, in fact, significantly decreased the sodium appetite stimulating effect of reduction of CSF [Na] in the Na-deplete animal.

Angiotensin II↗

PubMed1987

Inhibition of dehydration induced drinking in rats by reduction of CSF Na concentration.

Male rats were dehydrated for 22 h and then given 4 h intracerebroventricular (i.c.v.) infusions which commenced 2 h prior to the beginning of a 2-h fluid access period. I.c.v. infusion of iso-osmotic 0.27 M mannitol-CSF more than halved the amount of water normally drunk by dehydrated rats during the fluid access period. Whilst i.c.v. infusion of 0.7 M mannitol-CSF did not alter the amount of water drunk during the fluid access period. Presumably both infusates reduce CSF [Na] but only 0.7 M mannitol elevates CSF osmolality. The evidence is consistent with the involvement of both sodium and osmoreceptors in thirst in the rat. A reduction of CSF [Na] will inhibit dehydration induced water drinking provided the osmotic pressure of the CSF is not greatly elevated. In addition evidence is provided to show that a contrived reduction of CSF [Na] alone is not a sufficient physiological trigger to initiate salt appetite in rats.

Animals↗

PubMed1987

Water drinking caused by intracerebroventricular infusions of hypertonic solutions in cattle.

Infusions into the lateral cerebral ventricle of hypertonic solutions of NaCl, mannitol or sucrose all induced water drinking in cattle. However, infusion of hypertonic NaCl caused a significantly greater water drinking response than did the infusions of mannitol or sucrose, despite the fact that CSF osmolality increase was similar. In contrast, hypertonic solutions of NaCl or mannitol had similar dipsogenic effects when infused intravenously. The intracerebroventricular infusions of hypertonic NaCl or mannitol did not affect the intakes of food or Na solution. The results are consistent with the hypothesis that both cerebral osmoreceptors and Na sensors are involved in regulating thirst in cows.

Animals↗

PubMed1987

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)

Angiotensin II↗

PubMed1987

The role of taste in rapid sodium satiation by sodium-deficient sheep.

Sheep with a parotid fistula and sodium-deprived for 24 or 48 h (Na deficit = 500-700 mmol) were trained to drink their entire requirement of sodium bicarbonate solution from a cup in their cage in a single draught for up to 2 min. The cup was connected to a reservoir by an apparatus that enabled the concentration of the solution offered to be changed after the animal had drunk the first 100 or 150 ml of fluid without interrupting the flow of fluid or disturbing the drinking sheep. Under control conditions, the concentrations of solutions in the cup and reservoir were the same, either 900 mM or 300 mM NaHCO3. On experimental days, the concentration of NaHCO3 in the cup and reservoir were different so that the concentration of fluid increased from 300 mM to 900 mM or decreased from 900 mM to 300 mM NaHCO3. On those experimental days when the concentration of NaHCO3 was increased from 300 to 900 mM, the sheep drank a volume of fluid sufficient to maintain intake commensurate with loss. However, when the concentration of NaHCO3 was decreased from 900 to 300 mM, the sheep drank a volume of fluid insufficient to correct the deficit. It is proposed that the failure of sheep to react appropriately to a decrease in NaHCO3 concentration is a consequence of taste adaptation.

Animals↗

PubMed1987

Effect of variation of the composition of CSF in the rat upon drinking of water and hypertonic NaCl solutions.

Infusing conscious unrestrained rats with either 0.5 M NaCl-CSF or 0.7 M sucrose-CSF into the lateral cerebral ventricle (IVT) at 38 microliters/hr for 4 hr induced drinking. Although the infusates were nearly equiosmotic, water drinking during the 0.5 M NaCl-CSF was greater than during 0.7 M sucrose-CSF. However, IVT infusions of 0.7 M mannitol-CSF at rates of 9.4 microliters/hr or 38 microliters/hr for 4 hr or 10 microliters/hr for 4 days failed to induce water drinking. Also, IVT infusion of 0.27 M mannitol-CSF at 38 microliters/hr for 4 hr failed to significantly alter water drinking. CSF [Na] was reduced by IVT infusion of either 0.7 M sucrose-CSF or 0.7 M mannitol-CSF. In contrast, CSF [Na] was increased by 4-hr IVT infusion of 0.5 M NaCl in rats denied access to water during the infusion. Intake of 0.5 M NaCl was not altered significantly from control intakes by any of the above IVT infusions. It is concluded that water drinking in the rat may be initiated by stimulation of either a sodium sensitive sensor alone or with an osmoreceptor system and that species specific differences in the induction of both water drinking and hypertonic saline drinking are apparent.

Animals↗

PubMed1987

Cerebral osmoregulation of renal sodium excretion--a response analogous to thirst and vasopressin release.

Studies in sheep have shown that renal excretion of sodium may be under osmoregulatory control. When sheep become dehydrated, or are infused intravenously with hypertonic saline, they increase renal Na excretion in addition to secreting vasopressin and developing a thirst. These natriuretic, antidiuretic, and dipsogenic responses to dehydration and hypertonicity can be greatly reduced by lowering the cerebrospinal fluid NaCl concentration or by prior ablation of tissue in the anterior wall of the third ventricle. Lowering of cerebrospinal fluid NaCl concentration also prevents postprandial natriuresis which normally occurs in association with a postprandial increase in plasma Na concentration and tonicity. We propose that there is a cerebral osmoregulatory control of Na excretion which may interact with volume influences from the cardiovascular system to regulate renal Na output. The effector mechanism from brain to kidney mediating such cerebral control of Na excretion is probably hormonal.

Animals↗

PubMed1987

Role of angiotensin in sodium appetite of sodium-deplete sheep.

The role of the renin-angiotensin system (RAS) in the Na appetite of Na-deplete sheep was investigated. Intravenous infusion of the angiotensin-converting enzyme inhibitor, captopril, at 0.01 or 0.1 mg X kg-1 X h-1 did not cause any change in Na intake, although the higher dose caused a marked decrease in mean arterial blood pressure. Intravenous infusion of captopril at 1.0 mg X kg-1 X h-1 over 24 h decreased Na intake by 45-55% in the absence of any change in Na loss. The decrease in Na intake was restored to base-line level or above by concurrent intravenous infusion of angiotensin II (ANG II) at 3.8 or 24 micrograms/h over 24 h but not by intracerebroventricular (ICV) ANG II at 3.8 micrograms/h. In addition, ICV infusion of 0.7 M mannitol (1 ml/h over 3 h), which reduced cerebrospinal fluid (CSF) and brain extracellular fluid [Na], still increased Na intake when combined with intravenous captopril. Water intake was not altered during intravenous captopril or ANG II alone but was increased during ICV ANG II or 0.7 M mannitol (with or without iv captopril). In conclusion, these results suggest that the RAS is involved in the Na appetite of the Na-deplete sheep. Furthermore, it would appear that the brain area involved is one without a blood-brain barrier but with a CSF-brain barrier, such as one of the circumventricular organs. Also, it would appear that the effect of lowered cerebral Na and the effect of activation of the renin-angiotensin system on Na appetite are independent.

Angiotensin II↗

PubMed1987

On the brain involvement in saline loading natriuresis--an indirect evidence for the cerebral participation in the functional expression of the atrial natriuretic system.

The ablation of the anterior third cerebral ventricle region totally prevented the homeostatically effective natriuresis which should have followed hypertonic saline loading in conscious sheep. The increased cerebrospinal fluid (CSF) sodium concentration potentiated, and the decreased CSF[Na] prevented, natriuresis during isotonic saline loading. It is thus probable that a cerebral natriuretic system is involved in the functional expression of any other peripheral natriuretic system, e.g. the heart atrial natriuretic system which has been found to play a role in both hypertonic and isotonic saline loading natriuresis.

Animals↗

PubMed1986

Cerebrospinal fluid pressure of anaesthetized rats during intracerebroventricular infusion.

Increases in cerebrospinal fluid pressure (CSFP) were measured in the lateral ventricle in barbiturate anaesthetized male Sprague Dawley rats during intracerebroventricular (IVT) infusions into the contralateral ventricle. IVT infusions of isotonic artificial CSF (art-CSF) solutions at 10 and 38 microliters/hr increased mean CSFP from control preinfusion level of 3.6 cm H2O to 4.6 cm H20 (n.s.) and 5.2 cm H2O (p less than 0.01) respectively with CSFP appearing to attain equilibrium after 30-60 min of infusion. IVT infusion of hyperosmolar art CSF solutions (saccharide and salt solutions of approximate 1000 mOsm/kg) at 38 microliters/hr resulted in a larger increase of CSFP which equilibrated at 8.5 cm H2O (p less than 0.001) after 90 min of infusion. It is suggested that on the basis of CSFP measurements in these and other experiments cited that IVT infusions be run at infusion rates of less than 40 microliters/hr to ensure minimal physiological change.

Animals↗

PubMed1986

The dipsogenic effect of intracerebroventricular infusion of hypertonic NaCl in the sheep is mediated mainly by the Na ion.

In order to examine the importance of the chloride ion in the dipsogenic effect of intracerebroventricular (ICV) infusion of hypertonic NaCl, the water intake in response to 30-min ICV infusions of hypertonic solutions of different Na salts (0.25 M NaCl, NaI, NaSCN and 0.125 M Na2S2O3), mannitol (0.5 M) and choline chloride (0.25 M) was studied in the sheep. All solutions of the Na salts caused significant water drinking compared with ICV control infusions of isotonic artificial cerebrospinal fluid (CSF), except Na thiosulphate (Na2S2O3), which was much less effective, even after equilibration of its osmolality with the other sodium solutions by adding mannitol (0.125 M Na2S2O3/0.25 M mannitol). An inconsistent and small intake of water was induced by ICV hypertonic mannitol and choline chloride. It is concluded that the dipsogenic effect of ICV infusion of hypertonic NaCl in the sheep is mainly caused by the increased Na rather than the Cl ion concentration or the hyperosmolality in the extracellular fluid of juxtaventricular brain tissue.

Animals↗

PubMed1986

Ablation of subfornical organ does not prevent angiotensin-induced water drinking in sheep.

The subfornical organ (SFO) and surrounding periventricular tissue were ablated in sheep. Such a lesion did not significantly reduce water drinking in response to intracarotid, intravenous, or intracerebroventricular infusions of [Val5]angiotensin II amide (ANG II) but caused reduced intake of water in response to intracarotid infusion of hypertonic saline. The dipsogenic response of these sheep to water deprivation for 3 days was similar to that of normal sheep subjected to water deprivation. Although the results are not conclusive in excluding the SFO from having a role in ANG II-induced drinking, they show that there are receptors outside the SFO sensitive to blood-borne ANG II that are involved in water drinking in sheep. The results also show that tissue in the SFO or its surroundings may be involved in drinking caused by acute hypertonicity.

Angiotensin II↗