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Biomedical subjects

A N Epstein

Publications and source records attributed to A N Epstein.

At least 73 records · Page 4Linked to original sources
PubMed1978

Petide antagonists of the renin-angiotensin system in the characterisation of receptors for angiotensin-induced drinking.

The two naturally occurring analogues of angiotensin II (AII), Asp1-Val5-AII and Asp1-Ile5-AII, were equally effective as intracranial dipsogens in the water-replete rat. Renin, synthetic tetradecapeptide renin substrate (SRS) and angiotensin I (AI) also produced copious drinking when injected into the brain, but the naturally occurring renin substrate of rat caused little drinking and was much less effective than SRS. Prior intracranial injection of pepstatin, a competitive antagonist of the renin-angiotensinogen reaction, reduced drinking in response to renin and SRS but not to AI and AII. Renin-, SRS- and AI-induced drinking were inhibited by the converting enzyme inhibitor SQ 20881 injected through the same intracranial cannula in antagonist to agonist ratio of 1000:1, whereas the AII response was enhanced, although not significantly so, and the carbachol response was unaffected. Finally, position 8 aliphatic substituted analogues of AII were competitive antagonists of AII-induced drinking, and also inhibited drinking induced by renin, SRS and AI injected through the same intracranial cannula, but they did not inhibit carbachol-induced drinking. In conclusion, the angiotensin-sensitive receptor for thirst does not accept SRS or AI. It responds best to AII.

Angiotensin II↗
PubMed1978

Antidipsogenic role of the E-prostaglandins.

Prostaglandin E1 (PGE1) is antidipsogenic when administered into the lateral cerebral ventricle of the rat. In these experiments PGE1, at a dose of 1 microgram, suppressed water intake induced by centrally administered angiotensin II (AII) or carbachol, subcutaneously administered polyethylene glycol, and water deprivation. Even at this high dose, PGE1 did not reduce water intake due to cellular dehydration. As the dose of PGE1 was reduced, its suppressant effects became more specific to AII-induced drinking, with a dose of 10 ng yielding a significant suppression only in the case of AII-induced drinking. Even at a high dose (1 microgram), the PGE1 suppression of ingestion was specific to water intake. Although PGE1-treated rats reduced food intake if they were not hydrated prior to access to food, no reduction in food intake was seen when they received water by gavage before food presentation. Since PGE-like substances are synthesized in the brain, these data suggest the possibility that the prostaglandin may be involved in the regulation of water balance as a component of a reciprocal system in which water intake initiated by the activation of the renin-angiotensin system is halted by the synthesis and release of PGE.

Angiotensin II↗
PubMed1978

Localization of receptors for the dipsogenic action of angiotensin II in the subfornical organ of rat.

The proposal of the subfornical organ (SFO) as a site of receptors for drinking induced by angiotensin II (AII) was investigated with several mutually confirmatory experiments. Intracranial injections of physiological doses of AII elicited drinking if and only if applied directly to the SFO (Experiment I). Ablation of the SFO selectively (Experiment 2) and permanently (Experiment 4) eliminated drinking elicited by physiological doses of intravenously infused AII. Animals in which SFO had been ablated responded normally to cellular dehydration but reduced responding to the extracellular thirsts of beta-adrenergic activation and hyperoncotic colloid dialysis (Experiment 3). Infusion of saralasin, an AII antagonist, directly into the SFO selectively and reversibly antagonized intravenous AII drinking (Experiment 5). The hypothesis that the SFO contains dipsogenic receptors for circulating AII is strongly supported.

Angiotensin II↗
PubMed1976

Ontogeny of thirst in the infant rat.

The development of water drinking in response to thirst stimuli was found to be precocious and sequential in the neonatal rat. It was studied in suckling rats with a technique that took advantage of their vigorous consummatory reflexes and minimized appetitive responding. Responsiveness to the following thirst challenges appeared in the suckling rat with a clear timetable: cellular dehydration at 2 days of age, hypovolemia induced by colloid dialysis at 4 days, and beta-adrenergic activation at 6 days. Responsiveness to deprivation from mother's milk was vigorous at the earliest day tested (2 days) but could not be distinguished from hunger. Rats weaned, isolated, and tested as miniadults responded appetitively to thirst challenges as early as 16 days of age. But they required a warm environment, optimum access to the water source, and sufficient time to respond. As revealed by consummatory responding, the controls of water drinking mature weeks before they are required. They precede the maturation of capacities for sustained appetitive responding. These appear in the last week of the suckling period, yielding animals that are prepared for adult, thirst-motivated behavior at the onset of weaning.

Animals↗
PubMed1975

The cerebral ventricles as the avenue for the dipsogenic action of intracranial angiotensin.

Using low doses of angiotensin II (1-128 ng), a mapping study was carried out to redefine the region within the brain from which the dipsogenic response can be elicited. The most sensitive sites were either close to the anterior cerebral ventricles or were at the tips of cannulae that traversed a ventricular space en route to the tissue site. Conversely, insensitive sites were remote from the ventricles and were not reached by cannulae with a ventricular trajectory. Therefore, a thorough assessment of the role of the ventricular system in the angiotensin thirst phenomenon was demanded. Further studies revealed that direct intraventricular injections were as effective as those made into any tissue site tested. Also, regardless of the similarity in the sites of their termination, cannulae which passed through a ventricular space en route to that site yielded highly sensitive preparations whereas those which did not were insensitive to the hormone. Autoradiographic and radioassay studies showed that tritiated angiotensin II injected into anterior diencephalic tissue through cannulae which traversed the ventricles was rapidly distributed throughout the ventricular system. Thus, efflux of the injected material up the cannula shaft and its entry into the ventricular system is essential for a dipsogenic response to low doses of the hormone. These results support the hypothesis of a periventricular receptor site for angiotensin. It is suggested that systemically generated angiotensin and angiotensin endogenous to the brain may use the ventricular route as a means of access to the sensitive periventricular site.

Angiotensin II↗
PubMed1975

Control of meal size by central noradrenergic action.

Previous investigations of central noradrenergic effects on food intake have concentrated on the use of high doses of noradrenaline (two to 200 times brain noradrenaline content). In this work we examined the effect of low doses of noradrenaline (not exceeding brain noradrenaline content) on the parameters of spontaneous ingestive behavior. By arranging for rats to trigger remote infusions of noradrenaline into their own anterior forebrains at the beginning of spontaneously initiated meals, meal size was very reliably increased more than 200% by doses of 0.015--0.37 nmol (2.5--62 ng of noradrenaline base) (n = 12). The effect was alpha-adrenergic. It was blocked by phentolamine but not by propranolol. Infusions of noradrenaline at the above doses, which nearly triple meal size, did not elicit eating when made during an intermeal interval, nor did they influence the length of the intermeal interval when made 60 min after the termination of an uninfused meal. These results show that noradrenaline increased food intake at doses less than 1% of the brain's endogenous noradrenaline content. Meal size is more susceptible to alteration by noradrenaline manipulations than is meal frequency. The brain's own noradrenergic system may function to sustain food intake once feeding is initiated. This function of brain noradrenaline may control spontaneous meal size.

Animals↗
PubMed1975

Feeding induced by intracerebroventricular 2-deoxy-D-glucose in the rat.

Feeding was induced with lateral intracerebroventricular (ICV) injections of 2-deoxy-D-glucose (2-dg), a glucose analogue causing glucoprivation. Feeding increased rapidly by an average of 2.6 g following ICV 2-DG (2.9 or 5.8 mg per rat), but did not increase after ICV D-glucose or sucrose. At the same doses, 2-DG did not increase feeding when given peripherally. Core temperature dropped in a dose-dependent manner with doses of 2-DG sufficient to induce feeding after peripheral administration, but did not occur with ICV injections. The 2-DG (0.006--1.219 M) did not stimulate feeding when infused bilaterally into the lateral hypothalamus, the preoptic area, or the anterior lateral hypothalamus. Nor did it produce feeding when injected into the ventromedial hypothalamus at the same sites and in the same rats in which procaine HC1 caused increased feeding. The brain, therefore, is directly sensitive to glucoprivation in the control of feeding, and glucoprivation alone is sufficient to mobilize feeding behavior. The specific site of sensitivity to glucoprivation and the mode of action of the glucoprivic system in the brain are unknown.

Animals↗