Biomedical subjects

A N Epstein

Publications and source records attributed to A N Epstein.

At least 37 records · Page 2Linked to original sources

PubMed1990

Angiotensin/aldosterone synergy governs the salt appetite of the pigeon.

Sodium-replete pigeons drink excess 3% NaCl following concurrent treatment with both i.m. deoxycorticosterone acetate and pulse i.c.v. (p.i.c.v.) angiotensin II. This is not just a consequence of the water intake induced by p.i.c.v. angiotensin II, since the tachykinin eledoisin, given at equidipsogenic dose, does not evoke intake of salt. On the other hand, salt intake is not aroused in the sodium replete pigeon by continuous i.c.v. (c.i.c.v.) infusion of hyperosmotic mannitol (0.7 M) and c.i.c.v. infusions of hyperosmotic NaCl (0.3 M) or mannitol have no effect on the salt intake of the sodium deplete pigeon, or have effects that are unrelated to brain sodium. The salt appetite of the pigeon, like that of the rat, is evoked by an angiotensin and aldosterone synergy, and the angiotensin/aldosterone mechanism may be the general vertebrate theme of this behavior.

Aldosterone↗

PubMed1990

Dependence of adrenalectomy-induced sodium appetite on the action of angiotensin II in the brain of the rat.

Adrenalectomized rats express a robust sodium appetite that is accompanied by high levels of blood-borne angiotensin II and is caused by angiotensin II of cerebral origin. Blood-borne angiotensin II is elevated in rats consuming NaCl after adrenalectomy, and plasma angiotensin II concentrations are increased further when the animals cannot drink a NaCl solution. These phenomena are the result of the pathological removal of aldosterone, because replacement therapy returned both sodium intake and plasma angiotensin II concentrations to preadrenalectomy levels. The adrenalectomized rat's appetite for sodium is completely suppressed by interference with the central, but not the peripheral, action of angiotensin II. These data demonstrate that the mechanism of the sodium appetite of the adrenalectomized rat is a pathological instance of the angiotensin/aldosterone synergy that governs the sodium appetite of the adrenal-intact, sodium-depleted rat. Because aldosterone has been removed, angiotensin acts alone to produce the appetite. Furthermore, the data show that it is angiotensin II of central origin that is important for sodium appetite expression.

Adrenal Glands↗

PubMed1990

Brain glucoprivation and ketoprivation do not promote ingestion in the suckling rat pup.

We examined the possibility that brain glucose or ketone availability may control suckling or precocious feeding in the preweanling rat. Brain glucoprivation induced by 5-thio-D-glucose injection into the 4th ventricle did not increase feeding on orally infused milk until 30 days of age, although hyperglycemia was evoked as early as 9 days by the same treatment. Plasma ketone levels varied with suckling status, but pharmacological blockade of hepatic free fatty acid oxidation, which restricts ketone availability (ketoprivation), failed to increase suckling. Because the suckling rat can switch energy substrates under nutritional duress, we combined glucoprivation and ketoprivation. Feeding was suppressed, and suckling was not affected. Finally, we injected ketones into the 3rd brain ventricle and found that they increased feeding. Thus, in contrast to the adult rat, reduced glucose or ketone utilization by the brain does not increase food intake in the preweanling, but increased circulating and brain ketone concentrations may arouse feeding.

Animals↗

PubMed1989

The medial amygdala is part of a mineralocorticoid-sensitive circuit controlling NaCl intake in the rat.

Damage in female rats to the medial region of the amygdala abolished the sodium appetite that is evoked by mineralocorticoids (both aldosterone and deoxycorticosterone) without preventing the sodium appetite induced by body sodium depletion. It also eliminated or reduced the daily-need free saline intake of the female rat. These results suggest that the medial region of the amygdala is part of a specifically mineralocorticoid-sensitive neural circuit subserving sodium appetite.

Aldosterone↗

PubMed1989

Ontogeny of renin-induced salt appetite in the rat pup.

Intracerebroventricular injections of renin in suckling rat pups increased intake of NaCl solutions when they were orally infused 5 hr after injection. The appetite for saline solution was evident in pups as young as 3 days, was greater in females, and was specific insofar as intake of milk, either by suckling or by oral infusion, was not affected. Three-day-old pups increased intake only to 12% NaCl, the acceptable concentration of NaCl becoming lower in older pups. These results suggest, first, that, as is true for feeding and drinking, the brain mechanism for salt appetite is competent for expression of the behavior in the very young rat pup, and second, that its angiotensinergic neural substrate is distinct from that which mediates the dipsogenic effect of the hormone.

Animals↗

PubMed1989

Suppression of salt intake in the rat by neurokinin A: comparison with the effect of kassinin.

The present study investigates the effect of the mammalian tachykinin neurokinin A on salt intake in the rat. Intracerebroventricular injection of neurokinin A inhibited salt intake elicited by sodium depletion, by subchronic deoxycorticosterone treatment and by adrenalectomy. It also inhibited the need-free salt intake of female rats that had been previously depleted of sodium. Since different brain mechanisms elicit salt intake in these experimental models, it is concluded that neurokinin A exerts a general antinatriorexic effect. Apparently, its inhibitory effect on salt intake is not due to malaise or competing behaviors, as shown by the fact that the doses of neurokinin A which suppress salt intake do not suppress milk intake. In comparison to the amphibian tachykinin kassinin, neurokinin A possesses a similar spectrum of antinatriorexic activities, but is markedly less potent and less effective in all the experimental models investigated. These findings suggest that activation of neurokinin A receptors cannot solely account for the potent antinatriorexic effect of kassinin and of other nonmammalian tachykinins.

Adrenalectomy↗

PubMed1989

Prior episodes of sodium depletion increase the need-free sodium intake of the rat.

Prior episodes of sodium depletion increase the daily 3% NaCl intake of rats. They ingest large volumes and continue to do so for as long as 3 months after recovery from sodium deficit while eating sodium-rich food and while plasma sodium concentration and renal function are normal. The increased daily intake of sodium is, therefore, need-free. There is a marked sex difference in the need-free intake of 3% NaCl. Female rats drink more salt than do male rats when they are sodium replete and depletion naive. Repeated depletions raise the need-free intakes of both sexes but the effect is greater in females. Plasma concentrations of angiotensin II and aldosterone, which are markedly elevated by each episode of sodium depletion, return to basal levels between and after depletions, and are not the cause of the chronically increased need-free salt intake of the multi-depleted rat. These results suggest that the persistent increase in daily 3% NaCl intake that occurs in the rat with a history of repeated sodium depletions is a permanent, nonpathological increase in avidity for the taste of salty substances that results in life-long overconsumption of salt.

Aldosterone↗

PubMed1989

A role for the medial region of the amygdala in mineralocorticoid-induced salt hunger.

Damage to the medial region of the amygdala abolished aldosterone-induced salt hunger in the rat. In contrast, the salt hungers that are induced by adrenalectomy or by acute sodium depletion are left intact by the same brain damage. We suggest (a) that we have identified part of the neural circuit by which aldosterone participates in the genesis of salt hunger in the intact, sodium-depleted rat and (b) that these results provide further evidence for the hypothesis that there are separate receptive systems in the brain for the participation of aldosterone and angiotensin in the arousal of salt hunger.

Adrenalectomy↗

PubMed1988

Inhibitory effect of kassinin on salt intake induced by different natriorexigenic treatments in the rat.

Pulse intracerebroventricular (i.c.v.) injection of kassinin, 100-500 ng/rat, potently inhibits salt intake induced by sodium depletion. The effect appears to be selective since the same doses of kassinin do not inhibit milk intake or solid food intake. When given by continuous i.c.v. infusion kassinin elicits a clear anti-natriorexic effect at doses of 1-10 ng/min/rat. Kassinin not only suppresses sodium depletion-induced salt appetite, but it also inhibits sodium intake induced by pulse i.c.v. injection of renin or by subcutaneous (s.c.) deoxycorticosterone. Finally it also suppresses the elevated need-free intake of 1.5% NaCl in multidepleted female rats, which is not mediated by the renin-angiotensin-aldosterone system. These findings show that kassinin exerts a general suppressive effect on salt intake, irrespective of the natriorexigenic treatment. The present study suggests that the kassinin-like peptides that are endogenous to the rat brain may be involved in the behavioral regulation of extracellular body fluids in the rat by inhibiting sodium intake.

Animals↗

PubMed1988

The ontogeny of drinking evoked by activation of brain angiotensin in the rat pup.

Renin (1 ng) was injected into the 3rd ventricle of the brain of rat pups at various ages, and their ingestion was measured by weighing them either after 40 min of oral infusion of water or milk while they were away from their dam (off-dam), or after 40 min of suckling from their dams (on-dam). Beginning at 3-5 days of age, renin increased ingestion of milk and water off-dam. After 15 days of age, milk ingestion off-dam was no longer increased by renin, but intake of water continued to be evoked. In contrast, renin did not increase intake by suckling at any age. These findings reveal that the adult characteristics of the dipsogenic action of the renin-angiotensin system in the brain emerge at 15 days, at which age the increased intake becomes entirely specific for water. This finding confirms the precocity of the neural controls of drinking in the rat and shows that, like the controls of independent feeding, they are dissociated from those of suckling. It adds support to the idea that the neonatal mammalian brain contains separate neurological systems for suckling and for independent ingestion.

Age Factors↗

PubMed1988

Thirst-induced anorexias and the ontogeny of thirst in the rat.

In previous work (Leshem, M., Boggan, B., and Epstein, A.N. (1988). The ontogeny of drinking evoked by activation of brain angiotensin in the rat pup. Dev. Psychobiol. Vol.21, pp. 63-75) we showed that thirst elicited by activation of the brain's renin-angiotensin system in the suckling becomes specific to water after 16 days of age. However, in the suckling, we did not find the anorexia that reportedly accompanies angiotensin-induced thirst in the adult. This suggests the existence of a further stage in the ontogeny of thirst. Therefore, the present study pursued the ontogeny of thirst and its effects on milk intake through prepubescence into adulthood. Experiment 1 revealed that intracranial renin does not cause an anorexia to milk in prepubescent or adult rats. Experiment 2 showed that the absence of anorexia is true of thirst induced by renin but not by cellular dehydration, although both dipsogens suppressed milk intake when rats also had water available. Experiment 3 confirmed that the preweanling shows anorexia to solid food, as does the adult. Together with other work, these findings suggest that the ontogeny of the thirsts aroused by renin or intracellular dehydration is complete before weaning.

Aging↗

PubMed1988

Ontogeny of alpha- and beta-adrenergic anorexia in rats.

The anorectic action of alpha- (phenylephrine) and beta- (isoproterenol) adrenergic agonists was studied in mildly deprived neonatal, weanling, prepubescent, and adult rats. Intraperitoneal phenylephrine produced a reduction of food intake at all ages but with reduced potency and with a maximum of 50% in neonates. Contrary to intramuscular epinephrine that has no effect on feeding at any age, intramuscular phenylephrine was as effective as intraperitoneal in neonates, probably because it is not as rapidly destroyed in tissues as epinephrine. However, in weanlings and adults intramuscular phenylephrine was much less anorectic than intraperitoneal, suggesting that this effect is exerted via the liver. Isoproterenol did not reduce milk intake at any age before adulthood. Lactate had no effect on milk intake before the age of 40 days. Thus catecholamine anorexia is a purely alpha-adrenergic effect in young rats and appears before the metabolic effect of lactate. beta-Adrenergic anorexia, on the other hand, can be obtained only after puberty, suggesting that the mechanism mediating it matures after the preparatory action of the sexual hormones.

Aging↗

PubMed1987

The apparent dependence of salt appetite in the pigeon on endogenous angiotensin II.

Blockade of endogenous angiotensin II (ANG II) biosynthesis by intramuscular administration of the angiotensin converting enzyme inhibitor captopril (1 or 10 mg/kg b.w.t.) completely suppressed salt appetite induced by sodium depletion in the pigeon. The effect was selective since captopril did not reduce deoxycorticosterone (DOCA)-induced salt appetite nor water drinking to ANG II and eledoisin. Blockade of brain ANG II receptors by pulse intracerebroventricular (pICV) injection of the ANG II receptor antagonist [Sarcosine1, isoleucine8] ANG II produced a marked, although partial, inhibition of salt appetite. The inhibition was quantitatively similar to the effectiveness of the ANG II receptor blockade, as measured by the suppression of drinking to pICV ANG II. Blockade of brain aldosterone (ALDO) receptors by pICV injections of the mineralocorticoid receptor antagonist RU-28318 did not significantly suppress depletion-induced appetite at doses that markedly reduced DOCA-induced salt appetite. These findings suggest that the pigeon might be completely dependent on ANG II for the expression of depletion-induced salt appetite. This is in contrast with what has been found in the rat, in which blockade of both ANG II and ALDO are necessary to suppress the appetite.

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1987

The ontogeny of the antidipsogenic effect of eledoisin and physalaemin in the rat.

The ontogeny of the antidipsogenic effect of the tachykinins eledoisin and physalaemin was studied in 1- to 12-day-old Wistar rats. Both peptides inhibited drinking evoked by ICV angiotensin II, cell-dehydration or fluid deprivation. The effect of eledoisin appeared earlier than that of physalaemin (third v. sixth day) and was evoked by lower doses (10-100 ng/rat vs 330-1000 ng rat). The two tachykinins also inhibited milk intake, but this effect occurred only in the earliest days of neonatal life. The results confirm the specificity of the antitipsogenic effect of eledoisin and physalaemin and give further support to the hypothesis that brain tachykinins play a physiological role in the control of fluid intake.

Angiotensin II↗

PubMed1987

Salt appetite is enhanced by one prior episode of sodium depletion in the rat.

A single sodium depletion enhances the salt appetite that is expressed after a second and subsequent sodium depletions. The enhanced salt intake, as measured by a decrease in latency to drink and an increase in volume of 3% NaCl ingested, is not accounted for by an increased sodium loss. The enhanced salt intake occurs even when the interval between first and second depletion is as long as 4 months. The enhanced salt appetite does not depend on the drinking of salt after the animal's first sodium depletion and is specific for NaCl but not for KCl. Moreover, it can be produced without sodium depletion by the actions of the hormones aldosterone and angiotensin on the brain. These results suggest that angiotensin and aldosterone, which are released in response to sodium depletion, (a) increase renal sodium conservation, (b) evoke a salt appetite to restore the lost sodium, and (c) produce enduring changes in the brain that prepare it for more rapid and more vigorous expression of salt appetite in response to future sodium depletions. Thus the neural mechanisms that govern salt appetite are not only activated by the hormones of sodium conservation but appear also to be organized by them for a lifelong increase in avidity for salty substances.

Animals↗

PubMed1987

Salt appetite in the pigeon in response to pharmacological treatments.

1. In response to furosemide-induced sodium depletion pigeons showed a robust salt appetite. Following the 1st depletion they started to ingest 3% NaCl after a latency of 373 +/- 69 s and in 24 h they took 21.16 +/- 3.07 ml of this solution (vs. a daily mean intake of 1-2 ml prior to the depletion). 2. The appetite was selective as shown by the fact that when, after depletion, 0.34 M-CaCl2 was offered (which is equiosmotic to 3% NaCl) pigeons took just a trivial amount of it. 3. Analysis of sodium losses following the natriuretic treatment revealed that pigeons respond to sodium depletion with an excessive overconsumption of NaCl solution. In the 2 h after access to salt they took about 3 times the amount of sodium lost. 4. Repeated sodium depletions sharply reduced the latency to the ingestion of salt and produced larger intakes. However, the overall amount of salt taken in 24 h after the later depletions was very similar and statistically indistinguishable from that taken following the 1st depletion. 5. Subchronic deoxycorticosterone acetate treatment (2 mg pigeon-1 day-1 I.M.) increased daily 3% NaCl intake, but large variability was observed in the response. 4 mg pigeon-1 day-1 evoked a reliable 3% NaCl intake which was particularly marked from the 5th day of the treatment. 6. Pulse intracerebroventricular (I.C.V.) injection of purified hog renin evoked water intake within about 1 min of injection, followed (about 6 h later) by increased salt intake. In the 24 h after renin injection pigeons took 16.58 +/- 2.89 ml of 3% NaCl. On the 2nd day following injection salt intake was still higher than in controls. 7. In conclusion, our results show that pigeons respond to sodium depletion with a robust salt appetite. Moreover, salt appetite can be evoked by deoxycorticosterone acetate as well as by renin. These findings suggest that in the pigeon salt appetite may be an endocrine-induced behaviour controlled by mineralocorticoids and by the renin-angiotensin system.

Animals↗

PubMed1986

The role of the subfornical organ in the drinking behavior of the pigeon.

Pigeons with radiofrequency lesions that damaged the subfornical organ (SFO) (n = 4) or that isolated it from adjacent structures (n = 5), but not sham-lesioned pigeons, were unresponsive to blood-borne (i.p.) ANG II (100 micrograms/pigeon) in the immediate postoperative period and for 60 days thereafter. These animals were less sensitive to hypovolemic challenge (20% PEG), but they responded normally to 24 h of water deprivation and to cellular dehydration. Despite their unresponsiveness to bloodborne ANG II, the lesioned pigeons drank normally to 10 ng of i.c.v. ANG II given as early as 10 days after surgery, and they drank reliably and vigorously but less in total volume to 100 ng i.c.v. They also drank quickly, vigorously, and in normal total volume to i.c.v. tachykinins and bombesins, and to the peripheral (i.p.) bombesins. Peripheral (i.m.) tachykinins produced only low volume and variable drinking in all birds tested regardless of brain damage. The SFO of the pigeon, like that of the mammal, is essential for drinking evoked by blood-borne ANG II and is not necessary for thirst aroused by ANG II acting from within the cerebral ventricles. Lastly, it does not mediate the dipsogenic effects of the tachykinins or the bombesins.

Angiotensin II↗

PubMed1986

Suppression of drinking but not feeding by central eledoisin and physalaemin in the rat.

The tachykinins, eledoisin and physalaemin, given by intracerebroventricular (i.c.v.) injection have been shown to be potent antidipsogenic agents in rats. To evaluate their selectivity of action on rat ingestive behaviors, we compared their effects following i.c.v. injection on the intake of water, of milk containing 3.5 or 15% fat, and of solid food. The two tachykinins inhibited water intake induced by i.c.v. angiotensin II or by cellular dehydration, but did not reduce the intake of 15% fat milk or of solid food. The intake of 3.5% fat milk was inhibited only by the highest dose (1000 ng/rat) of eledoisin which also increased grooming and locomotion. The present findings suggest that in adult rats central eledoisin and physalaemin exert a selective suppressive effect on drinking behavior without affecting feeding.

Animals↗