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Biomedical subjects

N E Rowland

Publications and source records attributed to N E Rowland.

At least 127 records · Page 7Linked to original sources
PubMed1988

Comparison of the effects of the dipeptidyl peptidase inhibitors captopril, ramipril, and enalapril on water intake and sodium appetite of Sprague-Dawley rats.

Two experiments were performed with Sprague-Dawley rats to study the effects of different inhibitors of angiotensin I converting enzyme (ACE) on water intake and sodium appetite. Subcutaneous administration of low doses of either enalapril (MK421) or ramipril (Hoe498), like captopril, was dipsogenic. Acute administration of ramipril also enhanced the drinking response to peripherally administered angiotensin I (Ang I). Higher doses inhibited the drinking response to Ang I, administered acutely either peripherally or centrally. These data provide behavioral evidence that the nonsulfhydryl inhibitors enalapril and ramipril inhibit brain converting enzyme activity and that they are considerably more potent than captopril. All three of these compounds, administered chronically in food, induced an appetite for sodium chloride (NaCl) solution. Enalapril and ramipril were more potent than captopril. Plasma renin activity was increased by each of these inhibitors, but the magnitude of the increase was not clearly related to the amount of NaCl consumed. The water intake in response to acute administration of either Ang I or isoproterenol was not reliably increased in rats treated chronically with these inhibitors.

Angiotensin I↗
PubMed1988

Induction of an appetite for sodium in rats that show no spontaneous preference for sodium chloride solution--the Fischer 344 strain.

Fischer 344 rats show no spontaneous preference for isotonic sodium chloride (NaCl) solution. These experiments indicate, however, that a strong appetite for this solution may be induced by various methods, including adrenalectomy, administration of a mineralocorticoid hormone, acute depletion of sodium, and treatment with inhibitors of the angiotensin I converting enzyme (ACE). These treatments were also shown to produce the expected changes in the renin-angiotensin-aldosterone system, which thus appears to be involved in the induction of an appetite for NaCl solution in this strain of rat. The intakes of NaCl induced in the Fischer 344 rats by these experimental paradigms are less than those that have been reported in either Sprague-Dawley or Wistar strains in similar paradigms. In the case of sodium depletion, the intake of NaCl solution by Fischer 344 rats appears to be more closely related to the deficit than in the other two strains. Thus, the Fischer 344 strain of rats may be a particularly good model for studies of need-related sodium appetite.

Adrenalectomy↗
PubMed1988

Characteristics of thirst and sodium appetite in mice (Mus musculus).

The intakes of water and sodium chloride (NaCl) solution were examined in mice following treatment with agents that either stimulate or mimic various components of the renin-angiotensin-aldosterone system. Injections of either angiotensin II (Ang II) or isoproterenol produced very little water intake compared with the robust responses to either intracellular dehydration or to extracellular dehydration induced by treatment with polyethylene glycol (PEG). In studies on appetite for NaCl solution, mice exhibited no spontaneous preference for 0.15 M NaCl solution over water and did not change this preference during treatment with deoxycorticosterone acetate (DOCA), a sodium-deficient diet, or after adrenalectomy. Plasma concentrations of aldosterone were increased in intact mice fed a sodium-deficient diet but were not eliminated by adrenalectomy. However, acute treatment with furosemide in combination with a sodium-deficient diet stimulated an appetite for NaCl solution. Chronic oral administration of an angiotensin I (Ang I) converting enzyme inhibitor failed to induce a NaCl appetite. These findings show that mice are refractory to the induction of either water or NaCl intake by stimuli of the renin-angiotensin-aldosterone system, stimulation that is highly effective in rats; this suggests that there may be major differences among rodents in the hormonal determinants of behaviors related to hydromineral homeostasis.

Angiotensin II↗
PubMed1988

Dexfenfluramine: effects on food intake in various animal models.

The effects of dexfenfluramine on food intake of rats are compared and contrasted among several paradigms. Paradigms that involve overfeeding rather than deprivation, show a greater effect of the agent. Furthermore, both stress-induced eating as well as a food-motivated response (running) are particularly sensitive to inhibition by dexfenfluramine. The results of chronic administration of dexfenfluramine on both behavior and neurochemistry are reviewed, with particular reference to brain 5-HT. The effects of dexfenfluramine on diet selection and conditioned preferences are discussed. Finally, we suggest that species differences may exist in either the neurochemical and/or behavioral responses to dexfenfluramine.

Animals↗
PubMed1987

Postingestional modulation of drinking induced in rats by angiotensin II: intragastric infusion and sham drinking studies.

The dipsogenic potency of angiotensin II (ANGII, 200 micrograms/kg, SC) was examined after the removal of various postingestional factors. In the first experiment, rats with intragastric catheters were injected SC with ANGII and allowed water to drink. During the induced drinking, either NaCl (1.5 M) or water was injected into the stomach via the catheter at a rate of 0.1 ml for each ml water ingested orally. The water intake was identical in the two conditions. In a second experiment, rats, fitted with gastric fistulas, were administered ANGII and subsequent water intake with fistulas open was compared to that occurring with the fistulas closed. Rats drank more water during the first trial with fistulas open than with fistulas closed. Water intake during subsequent trials with an open fistula rose above that observed on the first trial. In a third experiment, rats with gastric fistulas were offered 0.15 M NaCl to drink. Intake was greater when the fistula was open than when it was closed. Intake of 0.15 M NaCl increased during the second trial with fistula open. Rats drank more 0.15 M NaCl during the first trial with an open fistula in Experiment 3 than those rats given water to drink on their first trial with fistula open in Experiment 2. These data suggest both oropharyngeal and postingestional factors interact in the control of ANGII-induced fluid intake.

Angiotensin II↗
PubMed1987

Water intake induced in rats by serotonin and 5-hydroxytryptophan: different mechanisms?

The present studies were designed to investigate further the mechanism by which water intake is induced in rats by peripheral administration of either serotonin (5HT) or its precursor 5-hydroxytryptophan (5HTP). Consistent with previous studies that have implicated mediation by the renal renin-angiotensin system (RAS), we now report that bilateral nephrectomy completely abolishes the drinking response to various doses of 5HT. In contrast, nephrectomy had little effect on the drinking induced by 5HTP. Thus, 5HTP may induce drinking by mechanisms other than its peripheral conversion to 5HT and subsequent activation of the RAS. The drinking responses to both 5HT and 5HTP were blocked by peripheral administration of the 5HT receptor antagonist, metergoline, but the drug was at least ten-fold more potent against 5HTP than 5HT. Intracerebroventricular (ICV) administration of metergoline also prevented the drinking response to peripherally-administered 5HTP. The drinking responses to both 5HT and 5HTP were enhanced by peripheral administration of low doses of an angiotensin I converting enzyme inhibitor, captopril. Collectively, these findings support previous conclusions that 5HT-induced intake of water is mediated exclusively by the renal RAS. However, 5HTP-induced drinking may additionally involve a renin-independent, serotonin-mediated mechanism, possibly in the brain.

5-Hydroxytryptophan↗
PubMed1987

Re-examination of the effect of either a lateral or third ventricular cannula on captopril-induced salt appetite in rats.

In Study A, rats were implanted with a cannula aimed at either the lateral (LV) or ventral third (V3V) brain ventricles 1 week prior to starting a chronic oral regimen of captopril. The presence of neither cannula significantly impaired the emergence of captopril-induced appetite for NaCl solution. In Study B, V3V cannulae were implanted in rats after a captopril-induced appetite for NaCl was established. The surgery produced a 1-2 day attenuation of NaCl intake, but this was no greater than that observed in a sham-operated group that received no cannula. These results do not support those of others who suggest that captopril (and, by inference, other agents) can leak across a damaged blood-brain barrier for at least 2 weeks after placement of a cannula. Possible reasons for the differences in results are addressed.

Administration, Oral↗
PubMed1987

Water versus NaCl intake by rats administered certain dipsogens acutely.

Isotonic saline was ingested in a greater volume than water when any one of three dipsogenic agents [L-5-hydroxytryptophan (25 mg/kg, SC), isoproterenol (25 micrograms/kg, SC), and angiotensin II (100 micrograms/kg, SC)] was administered acutely to rats given either isotonic saline or water to drink. These results are consistent with, but not exclusive to, the hypothesis that feedback inhibition of ingested isotonic saline on further fluid intake is less than that of water. Additional studies showed that the dipsogenic response to angiotensin II (200 micrograms/kg, SC) decreased as the concentration of NaCl solution offered to drink increased beyond 0.15 M in rats given either water or NaCl solution to drink. This suggests the possibility that the intensity of taste of the NaCl solutions may be a factor in their intake under these conditions, although the intake of these salt solutions by untreated controls did not reflect this. When the rats were allowed to choose between either 0.15 or 0.25 M NaCl solution and water, administration of angiotensin II (either 100 or 200 micrograms/kg, SC) increased water intake in preference to the NaCl solution. These results suggest that the rat, under these conditions, has a preference for water over NaCl solution.

5-Hydroxytryptophan↗
PubMed1986

Effect of continuous infusions of dexfenfluramine on food intake, body weight and brain amines in rats.

The present experiments describe the effects of continuous SC infusion, via osmotic minipump, of dexfenfluramine on food intake and body weight of male and female rats. It was found that the food intake of male rats was reduced by infusions of both 3 and 6 mg/kg/day although tolerance developed within 2-4 days at the lower dose. Further, these rats showed tolerance to an acute anorectic test dose of dexfenfluramine. Body weight loss was sustained by both groups. In older (6-8 mo old) female rats, some of which had previously nursed three litters, the anorectic effects of dexfenfluramine (3 and 6 mg/kg/day) were sustained throughout the 6 day infusion, and weight loss was substantial. The effects did not differ between bred and virgin rats of comparable age. The lower dose of dexfenfluramine produced no depletion of brain serotonin (5HT), although 5HIAA was reduced. Both compounds were depleted by the higher dose. The 3 mg/kg/day dose, in select rat populations, may be a close model for the mode of dexfenfluramine administration to humans.

Amines↗
PubMed1986

Medial hypothalamic lesions in Syrian hamsters: characterization of hyperphagia and weight gain.

Syrian golden hamsters (Mesocricetus auratus) received bilateral lesions aimed at the ventromedial hypothalamus (VMH) or a sham lesion. In the first study, some of the animals in each surgical group were housed in standard sedentary conditions while others had free access to running wheels. The lesions produced a 30% increase in the daily intake of chow, and this was accomplished exclusively by increased meal sizes. As a result, lesioned hamsters gained body weight relative to controls both on the chow diet and in a subsequent high fat diet phase. The effects were comparable in both sedentary and exercising groups. The lesions produced increases in body length and fat content. In the second study, lesions were made in the VMH or in adjacent nuclei and, after an initial period on chow, the hamsters were then given a choice between chow and high fat diet. The lesioned hamsters showed no unusual preference for the high fat diet but, as before, those with damage to the VMH or paraventricular nucleus (PVN) showed exaggerated body weight gain. Hamsters with these lesions were hyperinsulinemic in both fed and fasted conditions at the end of the study.

Animals↗
PubMed1986

Effect of the presynaptic dopaminergic agonist, quinpirole, on the drinking responses of rats to angiotensin II, isoproterenol, and hypertonic saline.

The dopamine (DA2) agonist, quinpirole hydrochloride (LY 171555), has been reported to inhibit central presynaptic release of norepinephrine, an effect similar to that of clonidine, an alpha 2-adrenoceptor agonist. Since clonidine exerts an antidipsogenic effect on all types of laboratory-induced drinking, the objective of these experiments was to determine whether administration of quinpirole hydrochloride produced a similar effect. The drinking responses of rats to administration of angiotensin II (200 micrograms/kg, SC), isoproterenol (25 micrograms/kg, SC), and hypertonic saline (1 M NaCl, 1% of body weight, IP) were blocked by administration of quinpirole hydrochloride (7.5 mg/kg, IP). When administered alone, quinpirole had no effect on water intake. Thus, the antidipsogenic effect of quinpirole hydrochloride resembles that of clonidine and suggests that release of norepinephrine occurs centrally at some point along the final common pathway for drinking in rats.

Angiotensin II↗
PubMed1986

Do peripheral and cerebroventricular injections of angiotensin II act at the same site? Studies on additivity of drinking.

The urge of rats to drink following SC injections of angiotensin II (AII) far outlasts the relatively short half life of this hormone in the circulation. When water was withheld for 1 hr following SC administration of AII, water intake was similar to that of rats administered AII and given immediate access to water. Saralasin, the AII receptor antagonist, blocked this delayed drinking response, suggesting that AII receptor occupancy is critical to the appearance of the delayed drink. In contrast, the urge to drink following cerebroventricular (IVT) injection decayed within 30 min. Intravenous (IV) infusion of AII for 1 hr caused drinking during the infusion but, when water was withheld until the infusion had ended, the urge to drink decayed within 15-30 min. Additional studies tested the additivity of the drinking response to two separate doses of AII when administered peripherally and IVT. The combined administration of AII SC and IVT failed to produce clear signs of additivity over a large range of interstimulus intervals. In contrast, the combined administration of IV and IVT AII were clearly additive with respect to drinking.

Angiotensin I↗
PubMed1986

Effect of intragastric and intraperitoneal water and saline loads on the pharmacologic induction of drinking in rats.

Water intake, induced by subcutaneous (SC) administration of angiotensin II (AII, 200 micrograms/kg), isoproterenol (25 micrograms/kg), 5-hydroxytryptophan (25 mg/kg), and bethanechol (8 mg/kg), was reduced completely to control level by administration of either an intragastric (IG) or intraperitoneal (IP) load of distilled water (3% of body weight) prior to administration of the dipsogen. A similar load of isotonic saline given by both the IG and IP routes was either ineffective or only partially effective in reducing the dipsogenic response. The similar effectiveness of IP and IG loads of water in inhibiting the responsiveness to administration of dipsogenic agents argues against a gastrointestinal mechanism as an integral part of the feedback process limiting water intake in the rat. In addition, the lack of a significant effect of similar IP and IG loads of saline suggests that stretch of either the gastrointestinal or intraperitoneal spaces is not an important factor in the inhibition observed. A possibility exists that osmotic dilution, as a result of the water load, may play a role in the feedback inhibition of the drinking responses to the dipsogenic agents used in these studies, even though the responses were mediated via the AII receptor pathway rather than the osmoreceptor pathway.

5-Hydroxytryptophan↗
PubMed1986

Effect of intraperitoneal and intragastric loading with water and isosmotic solutions of saline and glucose on water intake of dehydrated rats.

Female rats, dehydrated with food available for 24 hr, lost 6 to 8% of body weight. When allowed access to water, 40 to 60% of the weight deficit was replaced within the first hr. Either intraperitoneal (IP) or intragastric (IG) water loads (3% of body weight) administered just prior to return of water inhibited water intake of dehydrated rats nearly completely during the first hr of access to water. In contrast, similar loads of isotonic saline were much less effective. Even when 0.5 and 1.0 hr elapsed between IP loading (3% of body weight) with isotonic saline and access to water, water intake was not significantly different from that of untreated, dehydrated controls. In contrast, a similar IP load of water at these times completely inhibited water intake. Because of the contrasting effects of similar loads of water and isotonic saline on water intake of dehydrated rats, additional studies were carried out with an isosmotic solution of glucose (5%). IG administration (3% of body weight) of glucose inhibited water intake of dehydrated rats. IP administration (3% of body weight) attenuated the drinking response but did not reduce it to the level observed in dehydrated rats given an IP water load. When isosmotic glucose was administered at 0.5, 1.0, and 2.0 hr prior to allowing access to water, water intake was reduced significantly below that of dehydrated controls and to the same extent regardless of time of administration of the glucose load.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Dietary self-selection in diabetic rats: an overview.

The literature concerning dietary self-selection patterns of diabetic rats is reviewed and compared with new data. There is agreement among the various investigators as to the dietary choices observed following induction of diabetes, regardless of the diabetogenic treatment used. That is, moderately diabetic rats select a high fat, low carbohydrate diet, whereas more severely diabetic animals consume high protein, low carbohydrate diets with little change in fat consumption relative to nondiabetic controls. Even very midly diabetic rats reduce carbohydrate intake. Evaluation of metabolic status of diabetics suggests that with severe diabetes, the beneficial reduction of plasma glucose seen with consumption of a high fat diet may be offset by extreme elevations in ketone and triglyceride levels. Moreover, the hypothesis that diabetic rats are insensitive to carbohydrate calories seems weakened by evidence of reduced food intake following carbohydrate consumption either in solutions or as a gastric load. These findings are discussed in terms of "dietary wisdom" as first proposed by Richter.

Animals↗
PubMed1986

Effects of fenfluramine on food intake, body weight, gastric emptying and brain monoamines in Syrian hamsters.

In the first experiment, dose-inhibition and -time functions are documented for the anorectic effects of d,l-fenfluramine in Syrian hamsters (Mesocricetus auratus). A dose of 20 mg/kg (IP) inhibited feeding for at least 2-4 hr. In the second experiment, chronic treatment of hamsters housed either in running wheels (exercise) or standard (sedentary) conditions with d,l-fenfluramine (20 mg/kg) produced an attenuation of weight gain relative to vehicle-treated controls. However, there was no differential weight loss in the exercising drug-treated group. This result was also obtained using 10 mg/kg d-fenfluramine. In the third experiment, d,l-fenfluramine greatly inhibited gastric emptying of a test meal in hamsters. In the fourth experiment, hamsters were found to sustain only small and transient decreases in brain 5HT and 5HIAA levels after acute or chronic treatment with d,l-fenfluramine. These findings are compared and contrasted with the known effects of fenfluramine in rats. It is concluded that there may be species differences in the impact of fenfluramine on brain function, and that this may not be in any simple way related to the anorexigenic action of this drug.

Animals↗
PubMed1986

Tolerance to fenfluramine anorexia: fact or fiction?

Recent findings in this laboratory with regard to tolerance to fenfluramine anorexia are reviewed with respect to generality of the behavioural phenomenon. A systematic relationship between initial body weight and fenfluramine-induced weight change in rats is described. The possible roles of peripheral factors in fenfluramine anorexia and tolerances, including gastric emptying and peripheral serotonin, are discussed. The role of central factors is also considered. It appears that fenfluramine, and possibly other anorectic agents have multiple sites of action and affect multiple behaviours. Some clinical implications are noted.

Animals↗