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N E Rowland

Publications and source records attributed to N E Rowland.

At least 109 records · Page 6Linked to original sources

Thirst and sodium appetite in Dahl rats.

In confirmation of a previous study, rats of the Dahl S and R sublines exhibited no spontaneous preference for dilute NaCl solutions and an aversion for isotonic and hypertonic NaCl solutions when they were offered in a 2-bottle choice with water. A hysteresis effect was observed when choice was offered between water and a descending series of concentrations of NaCl solution compared with a preceding increasing series. In response to either chronic dietary administration of an angiotensin I converting enzyme inhibitor (ACEI) or acute sodium depletion, rats of the R subline developed a strong NaCl appetite, but the S subline did not. In contrast, rats of both sublines showed an NaCl appetite in response to a regimen of deoxycorticosterone acetate (DOCA). In acute drinking tests, rats of the S subline drank less water than those of the R subline in response to administration of either isoproterenol, ACEIs, or hypovolemia. Both R and S sublines drank similar amounts of water after SC administration of angiotensins I and II, and hypertonic NaCl. Compared with R rats, S rats had lower plasma renin activity in several of the above conditions, and their decreased thirst and sodium appetite appears to be a direct result of an underactive renin-angiotensin system.

Animals↗

On the waterfront: predictive and reactive regulatory descriptions of thirst and sodium appetite.

The concepts of homeostasis and regulation are discussed and examples are given in which current regulatory models of ingestive behavior inadequately predict or explain the observed phenomena. The implications of this for the choice of experimental paradigms, and the interpretation of neurobiological data obtained therein, are discussed. Paradigms that allow the expression of behavioral strategies and learned responses may be biologically more relevant than the more popular but highly constrained "physiologic" paradigms.

Animals↗

Comparison of the dipsogenic responsiveness of Long-Evans and Sprague-Dawley rats.

The dipsogenic responsiveness of the Sprague-Dawley (albino) and Long-Evans (hooded) strains of rats was compared. The responsiveness of the angiotensin II pathway for induction of drinking was assessed by means of acute administration of the beta-adrenoceptor agonist, isoproterenol (25 micrograms/kg, SC), angiotensin I (150 micrograms/kg, SC), and angiotensin II (150 micrograms/kg, SC). The results show that rats of the Long-Evans (hooded) strain drink less water than those of the Sprague-Dawley strain in response to acute administration of either isoproterenol or angiotensin I. However, there was no difference between groups in water intake resulting from administration of angiotensin II. This suggests that the Long-Evans strain has less capacity to convert angiotensin I to angiotensin II than the Sprague-Dawley strain, but that responsiveness of the Long-Evans strain to angiotensin II is similar to that of the Sprague-Dawley strain. The responsiveness of the osmoreceptor pathway for induction of drinking was also assessed both by measurement of the drinking response to acute administration of hypertonic saline (1% body weight of 1 M NaCl solution, IP) and a 24-hour dehydration. The results show that rats of the Long-Evans strain drink less water in response either to administration of hypertonic saline or to dehydration than those of the Sprague-Dawley strain. This suggests that responsiveness to stimulation of the osmoreceptor pathway of the Long-Evans strain induces less drinking than in the Sprague-Dawley.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

Dexfenfluramine: action with estradiol on food intake and body weight in ovariectomized rats.

Previous work from this laboratory has shown that chronic administration of dexfenfluramine (DF) caused substantial weight loss in rats that were overweight 3-4 mo after ovariectomy (OVX), but not in OVX rats that were of normal weight, as a result of estrogen replacement. The present study was conducted to determine whether the enhanced weight loss in the former group is because of either overweight per se or an inhibitory effect of estrogen on DF. Starting either 0, 6, or 14 wk after OVX, when weight gain was zero, moderate, or near maximal, respectively, rats received a 12-day regimen of either estradiol or the oil vehicle and either DF (3 mg.kg-1.day-1 by osmotic minipump) or no drug. DF had no effect on either food intake or weight gain of groups treated during 0-2 wk after OVX but had significant anorectic and weight loss actions in groups treated 6-8 and 14-16 wk after OVX. Estrogen had a similar effect at all three times and in the 14-wk group produced an effect that was additive with that of DF. Measures of plasma glucose and triglycerides and adipose tissue lipoprotein lipase activity did not correlate with the effectiveness of the drug to promote weight loss.

Adipose Tissue↗

Long-term actions of d-fenfluramine in two rat models of obesity. II. Responses to stress.

In the previous study (part I), we reported that a 28-day regimen of d-fenfluramine administered via osmotic pump sustained weight reductions in normal weight and obese rats without depleting brain 5-HT. Peripheral actions of d-fenfluramine were also examined. Here we extend those findings to night-time observations and to stressful conditions. This treatment regimen had no effects on night-time concentrations of insulin, triglycerides or corticosterone or on the stress-induced rise in triglycerides and corticosterone. The thermic response to cold was unaltered. Glucose tolerance was enhanced in lean, but not obese rats.

Animals↗

Effect of chronic administration of dexfenfluramine on stress- and palatability-induced food intake in rats.

Dexfenfluramine, administered chronically either SC via osmotic minipump (3 mg/kg/day) or as daily IP injections (1.5 mg/kg) to rats, suppressed tail pinch-induced eating for up to 14 days. The minipump regimen also caused a reduction of intake of a palatable "dessert" for up to 9 days in heavy, adult rats, but was only transiently effective in young, rapidly growing rats. Nonetheless, the regimen produced decreased weight gain and insensitivity to a subsequent acute test dose of the agent. These results illustrate the sustained anorectic efficacy of dexfenfluramine in paradigms that do not involve restriction of diet, and these may be animal models of snacking or binging. The data also corroborate previous suggestions that the agent is more effective in older or more obese populations.

Animals↗

Preference threshold for NaCl solutions and sodium homeostasis in hypophysectomized rats.

The NaCl preference threshold concentrations of male hypophysectomized (hypox) and intact rats were determined using a two-bottle choice paradigm. Although hypox rats ingested more total fluid daily (ml/100 g body weight), including water and NaCl solution, than intact rats, there were no significant differences between groups in either preference threshold (8.0 mEq/l) or preference maximum (90 mEq/l) concentrations. Further, the ratio of NaCl to total fluid ingested did not differ between hypox and intact groups throughout the large range of concentrations of NaCl solution presented to them. To assess their ability to conserve sodium, both intact and hypox rats were maintained on a sodium-deficient diet and distilled water for 3 days. Both groups reduced their urinary sodium outputs significantly compared to counterparts maintained on a sodium-replete diet. This suggests that the functional integrity of the renin-angiotensin-aldosterone system was maintained in the hypox rats. Resting plasma aldosterone concentrations, measured at the end of the experiment, did not differ significantly between groups. Assessment of completeness of hypophysectomy was made by measurement of daily urinary excretion of epinephrine and by change in body weight during the course of the experiment. Daily urinary excretion of epinephrine by hypox rats was reduced to one-tenth that of intact controls. Hypox rats also failed to grow during the course of the experiment. By application of both of these criteria, the rats were completely hypophysectomized.

Aldosterone↗

Effect of chronic dietary treatment with 1-tryptophan on spontaneous salt appetite of rats.

Chronic dietary treatment with 1-tryptophan (2.5 and 5.0% in food) reduced the exaggerated spontaneous NaCl intake induced by deoxycorticosterone acetate (DOCA) in rats. In the absence of DOCA, chronic (4-week) dietary treatment with 1-tryptophan (5.0% in food) failed to affect significantly spontaneous NaCl intake. In addition, treatment with tryptophan in the absence of DOCA failed to affect significantly systolic blood pressure, plasma renin activity, plasma aldosterone concentration, and the weights of the heart, kidneys, adrenals, and thyroid gland. It also failed to affect the specific binding of [125I]-Ang II to neuronal membranes isolated from the diencephalon of the rats. However, the contents of both serotonin and 5-hydroxyindoleacetic acid in the lower brain stem were increased significantly by chronic treatment with tryptophan. These results suggest that the effect of chronic treatment with tryptophan to reduce the salt appetite of DOCA-treated rats is a specific effect of this amino acid under these conditions and may be related to the ability of tryptophan to prevent the upregulation of specific Ang II receptors induced by DOCA.

Angiotensin II↗

Diabetes mellitus: stress, neurochemistry and behavior.

Neurochemical alterations in several rodent models of insulin-dependent diabetes are compared and their relevance to behavioral and physiological pathology in the clinical disorder is discussed. In the majority of rodent models, reductions in metabolism of norepinephrine (NE), dopamine (DA) and serotonin (5HT) in the central nervous system (CNS) have been reported. While there are two reports of increased 5HT turnover in CSF or post-mortem brains of diabetic humans experiencing severe ketoacidosis, these patients were receiving insulin therapy. Insulin appears to have effects on monoamines opposite to that of chronic hyperglycemia. Both in rodent models and in clinical populations, there is widespread evidence of enhanced hormonal and behavioral responsiveness to stress. There are findings in rodent models indicating that hormonal responses to stress are related to CNS monoamine activity. The mechanisms responsible for both hormonal and CNS alterations in diabetes, as well as their involvement in behavioral pathology, can best be investigated further using animal models.

Animals↗

Stress and behavior in streptozotocin diabetic rats: biochemical correlates of passive avoidance learning.

Retention of one-trial passive avoidance training was compared in diabetic and nondiabetic rats. Also compared were corticosterone concentrations associated with both training and retention testing, catecholamine excretion related to training, and regional brain catecholamine concentrations accompanying retention testing. Diabetic rats showed significantly better retention for the task than did nondiabetic rats. Associated with retention differences, diabetic rats had higher epinephrine excretion and nondiabetic rats had lower excretion after footshock training relative to baseline measures. Norepinephrine excretion was elevated in diabetics both in baseline measurement and during the 24 hr following footshock training. No differences were found in baseline or stimulated corticosterone concentration between diabetic and nondiabetic rats. Diabetic rats had higher concentrations of norepinephrine (NE) and dopamine (DA) and lower 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratios in hypothalamus and higher NE in brain stem and amygdala than did nondiabetics, although both diabetic and nondiabetic rats had reduced DA and NE following retention testing. The results indicate that there are biochemical alterations in diabetes that may have important behavioral impact.

Animals↗

Long term actions of d-fenfluramine in two rat models of obesity. I Sustained reductions in body weight and adiposity without depletion of brain serotonin.

In a treatment regimen designed to simulate clinical situations, d-fenfluramine was administered chronically (28 days) via osmotic minipumps to lean and obese female rats. Drug effects were assessed in dietary obese, ovariectomized obese, estradiol-treated ovariectomized and unoperated Chow-fed rats. Various central and peripheral effects of d-fenfluramine were measured and compared to effects of dietary restriction as well as posttreatment changes. d-Fenfluramine suppressed food intake and body weight in all but estradiol-treated rats and was especially effective in obese ovariectomized rats. This method of administration did not deplete brain 5-HT within 28 days. The measured drug actions that may be important in: appetite suppression and weight loss include chronic stimulation of brain 5-HT activity without depletion; stimulation of (Na+- K+)ATPase activity; reduction in lipoprotein lipase activity and effects on carbohydrate metabolism.

Adipose Tissue↗

[Serotonin, food intake and body weight].

Various animal models of hyperphagia and obesity have made possible the study of the effect on food intake of dexfenfluramine, an agent which both inhibits reuptake and stimulates release of 5 HT. These are chronic overfeeding models (hereditary model: Zucker rat, hormonal origin: insulin, ovariectomy, lesions of the VMH, and models including palatable and varied diet: cafétéria diet) and also acute overfeeding models (deprived rats, tail pinch, "dessert" test, metabolic or neuropharmacologic stimuli). Dexfenfluramine administered by osmotic minipump (3 mg/kg/day for up to 4 weeks) reduces food intake and produces weight loss in most of these models.

Animals↗

Behavioral and physiological aspects of body fluid homeostasis in Fischer 344 rats.

Previous studies have shown that Fischer 344 rats, unlike many other strains, have neither a spontaneous preference for dilute NaCl solutions nor an excessive consumption of it after sodium depletion. The present studies examine some characteristics of water intake in Fischer 344 rats. Their spontaneous water intake was only about 50% of that of age-matched Sprague-Dawley rats, and the water-to-food ratio was about 30% lower. When water was added to the food, Fischer 344 rats decreased their fluid intake by a corresponding amount, whereas Sprague-Dawley rats continued to drink substantial amounts. In the absence of food, Fischer 344 rats reduced their water intake by a greater fraction than rats of the Sprague-Dawley strain. Physiological changes during these studies were as expected from the behavioral data, except that plasma protein concentration was consistently 10% higher in Fischer 344 rats. In contrast to this economy in their spontaneous drinking, water intakes of Fischer 344 rats were comparable to Sprague-Dawley rats in response to water deprivation, and administration of either hypertonic NaCl or angiotensin II, and in a sham-drinking paradigm. However, following treatment with either isoproterenol or polyethylene glycol, Fischer 344 rats drank considerably less than Sprague-Dawley rats. Possible reasons for, and implications of, these strain differences in drinking are discussed.

Animals↗

Regulation of intakes of water and NaCl solutions in Fischer 344 rats: contrasts and comparisons between strains.

We present an overview of the differences in intakes of both water and NaCl between different strains of rat, with emphasis on Fischer 344 (F344) and Sprague-Dawley (SD) strains. Relative to SD, rats of the F344 strain show less spontaneous or secondary drinking both with food present and during food deprivation. The water intake of rats of the F344 strain is strongly inhibited when water is added to their food, but rats of the SD strain show less inhibition and consume excessive amounts of fluid. In studies of primary drinking, induced by treatment with various dipsogens, rats of the F344 strain consumed water in amounts that were generally comparable to those expected from rats of the SD strain, with the exception of reduced intakes in response to either polyethylene glycol-induced hypovolemia or treatment with isoproterenol. The hematocrit ratio, resting plasma renin activity and directly-measured plasma protein concentrations were similar between F344 and SD strains. We also review findings that rats of the F344 strain show no spontaneous preference for dilute NaCl solutions, and show that both a strong preference and a low preference threshold are induced by chronic treatment with ramipril. Other manipulations that induce an appetite for NaCl in the F344 strain are summarized.

Angiotensin II↗

Augmentation of isoproterenol-induced drinking by acute treatment with certain dopaminergic agonists.

Bromocriptine (1 mg/kg, IP), a dopaminergic agonist that crosses the blood-brain barrier, augmented the dipsogenic responsiveness of rats to acute administration of the beta-adrenergic agonist, isoproterenol (15 micrograms/kg, SC), when administered at the same time. When administered alone, it had no effect on either water intake or urine output. Dopamine (20 mg/kg IP), which does not cross the blood-brain barrier, also augmented the dipsogenic responsiveness to acute administration of isoproterenol. However, a major difference between the responses to bromocriptine and dopamine was that the latter augmented drinking only when administered 15 to 30 min prior to isoproterenol. During the 30 min between injection of dopamine and the injection of isoproterenol, output of urine and sodium increased approximately 6-fold above the level of controls such that the concentration of the urine excreted by the treated group was approximately isotonic. However, in spite of a 6-fold increase in output of urine by the treated, compared to the control group, dopamine-treated rats ingested water only to the same extent as untreated controls when access to water was allowed. This suggests that an isotonic contraction of extracellular fluid may not induce a dipsogenesis. It also suggests that the augmentation of isoproterenol-induced drinking by dopamine was not the result of a dehydration-induced drink superimposed on the isoproterenol-induced drink. The centrally and peripherally acting dopaminergic antagonist, spiroperidol (spiperone), inhibited the isoproterenol-induced drinking response in a dose-related fashion. However, the peripherally acting dopaminergic antagonist, domperidone,was without effect on isoproterenol induced drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Water intake of Djungarian and Syrian hamsters treated with various dipsogenic stimuli.

Djungarian and Syrian hamsters were found to exhibit robust water intake following water deprivation, and in response to hyperosmotic and hypovolumetric challenges to body fluids following injections of hypertonic NaCl and polyethylene glycol, respectively. Water intake was not stimulated following peripheral injections of isoproterenol, serotonin, or angiotensins II or III. Both hypovolema and isoproterenol activated the renin-angiotensin system. This profile of drinking responses in hamsters is similar to that reported previously for mice and degus.

Angiotensins↗

Sodium appetite: species and strain differences and role of renin-angiotensin-aldosterone system.

The characteristics of the appetite for NaCl in humans differ in some aspects from those in other species. The mechanisms of appetite for NaCl have been studied in detail in two species, rats and sheep. We review the treatments known to induce an appetite for NaCl in rats, with special reference to differences among strains in their spontaneous preference for NaCl solution. The current view of the mechanism is critically appraised, with particular emphasis on the role of angiotensin II, mineralocorticoids, cerebroventricular sodium transport, and the relation between preference for NaCl and the concentration of sodium in saliva. The appetite for NaCl in rodents other than rats is considered next, and reveals that mice, hamsters and gerbils are reluctant to ingest NaCl either spontaneously or after treatment with several of the natriorexigenic stimuli that are effective in rats. The characteristics of the appetite for NaCl in non-rodent species, including sheep, rabbit, dog, and non-human primates, are then described. We discuss some of the possible differences in mechanism that might account for this behavioral diversity among species.

Animals↗