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N E Rowland

Publications and source records attributed to N E Rowland.

At least 55 records · Page 3Linked to original sources
PubMed1996

Dissociation of Fos-like immunoreactivity in lamina terminalis and magnocellular hypothalamic nuclei induced by hypernatremia.

Rats were given either slow (1 h) or rapid (10 min) intravenous infusions of either 6 or 12 mmol NaCl/kg body weight. Fos-like immunoreactivity (FLI) induced by the infusions was measured in several brain regions. The higher dose of NaCl induced FLI in structures of the lamina terminalis, including organum vasculosum (OVLT) and subfornical organ (SFO), as well as in the magnocellular supraoptic (SON) and paraventricular hypothalamic (PVN) nuclei. The lower dose of hypertonic NaCl induced FLI in only the SON and PVN. Faster delivery of the solute load tended to amplify the FLI in SFO and OVLT. These data confirm and extend previous reports of osmotically-induced FLI in rat brain and demonstrate that the discrepancies between these studies result from different dosage regimens of NaCl. The data are discussed as they relate to the lamina terminalis as a primary osmosensitive region in brain.

Animals↗
PubMed1996

Centrally mediated vasodilation of the rat's tail by angiotensin II.

Acute peripheral administration of angiotensin II (AngII) to rats vasodilates the tail and reduces both metabolic rate and body temperature. To assess the role of the brain in these responses to AngII, a discrete lesion was aimed at the subfornical organ (SFO). Such lesions are known to abolish drinking and other responses to circulating AngII. A control group was sham-operated. Following recovery from surgery, dipsogenic responses to administration of AngII (150 micrograms/kg, SC) were tested. All lesioned rats failed to drink. One week later, the changes in colonic (TC) and tail skin (TSK) temperatures were measured following an identical injection of AngII. As reported before, control rats showed a substantial rise in in TSK (maximum rise 2.5 degrees C after 12 min). In contrast, the lesioned rats showed very little rise (0.3 degrees C) in TSK, significantly less than controls. The maximal drop in TC of the control group was slightly more (0.3 degrees C) than that of the lesioned group (0.2 degrees C), but the difference was not significant. The rats were, next, acutely exposed to cold (5 degrees C). Control rats showed a significantly larger decrease in TSK than lesioned rats. Lesions were verified both anatomically and using the functional metric of AngII-induced Fos-like immunoreactivity (Fos-IR). AngII induced strong Fos-IR in the SFO, median preoptic nucleus (MnPO), and in the magnocellular hypothalamic regions of control rats. The lesions ablated the anterior part of the SFO and dorsal MnPO, and greatly attenuated AngII-induced Fos-IR in the magnocellular hypothalamic regions. Thus, there appears to be central (SFO/MnPO) mediation of both the increase in TSK following administration of AngII and the decrease in TSK in the cold.

Angiotensin II↗
PubMed1996

Comparison of changes in blood pressure and dipsogenic responsiveness to angiotensin II in male and female rats chronically exposed to cold.

In most forms of experimentally induced hypertension in rats, females develop a less severe form of the disease than males. The objective of the present study was to compare the two genders with respect to the development of cold-induced hypertension. The results of the study indicate that both males and females develop comparable elevations of blood pressure and at approximately the same rate. Thus, the blood pressures of both groups increased significantly within 2 weeks of exposure to cold and reached similar maximal levels by the seventh week. The dipsogenic responsiveness of both groups of cold-exposed rats to acute administration of the peptide hormone, angiotensin II (AngII), was increased to approximately the same extent above that of warm-adapted counterparts, suggesting an increase in the responsiveness to AngII in the brain. To assess this possibility, the induction of the oncogene, cFos, was studied in brain following IV infusion of AngII (333 ng/kg/min). Fos-like immunoreactivity (FLI) was greater (p < 0.01) in subfornical organ, supraoptic and paraventricular hypothalamic nuclei of both cold-exposed groups compared to warm-adapted controls. Thus, both male and female rats have similar elevations of blood pressure as well as increased dipsogenic and FLI responsiveness to administration of AngII during chronic exposure to cold.

Angiotensin II↗
PubMed1996

The physiology and brain mechanisms of feeding.

This article is designed as an introduction to the major theoretical models in the field of regulation of eating behavior, and a selective review of relevant neurobiological data. We first critically consider the paradigm of homeostasis as it relates to body energy content, and argue that additional theoretical constructs will be needed to account for the complexity of eating behavior in both nonhumans and humans. We then summarize some of the methods available to the neuroscientist in this area, and address some of their limitations. We review treatments and potential mechanisms that increase food intake, including deprivation, antimetabolites, norepinephrine, and several peptides including neuropeptide Y. We next review treatments that decrease food intake, including a variety of humoral, gastrointestinal, and pancreatic factors, as well as examine central pathways of satiety. This includes a discussion of leptin and other potential anorectic agents. We conclude with a discussion of human obesity and anorexias, and prospects for pharmacotherapy of eating disorders. We emphasize throughout that most regions of the human brain probably make some contribution to feeding behavior, and so a focus on any one area of transmitter/hormone is an unrealistic approach both in basic and applied areas.

Animals↗
PubMed1996

Relationship between drinking and increase in tail skin temperature of rats treated with L-5-hydroxytryptophan.

Administration of L-5-hydroxytryptophan (25 micrograms/kg, s.c.), the immediate precursor of serotonin, to rats induces drinking and increases tail skin temperature. Decreases in both the metabolic rate (rate of oxygen consumption) and colonic temperature also occur. These responses are similar to those observed following acute administration of angiotensin II. However, both drinking and the increase in tail skin temperature are unaffected by prior administration of the non-peptide angiotensin II, AT-1 receptor antagonist, losartan potassium, but are partially attenuated by the beta-adrenoceptor antagonist, propranolol. This suggests that the responses are independent of the angiotensin AT-1 receptor but may be mediated, in part at least, by the beta-adrenoceptor. The hypothesis is presented that when either L-5-hydroxytryptophan or angiotensin II is administered to rats, they act centrally to reduce the set-point for body temperature regulation, thus resulting in the reflex activation of mechanisms that reduce body temperature, including an increase in tail skin temperature and a decrease in metabolic rate.

5-Hydroxytryptophan↗
PubMed1996

Regulation of norepinephrine transport system by angiotensin II in neuronal cultures of normotensive and spontaneously hypertensive rat brains.

Brain angiotensin II (Ang II) plays a key role in blood pressure control in part by interacting with catecholamines (CA) and by stimulation of sympathetic pathways. The significance of Ang-CA interaction is further heightened by the presence of a hyperactive brain Ang II system in spontaneously hypertensive (SH) rat, a genetic model for essential hypertension. Neuronal cells in primary culture from the hypothalamus-brainstem that mimic in vivo situations in so far as many cellular actions of Ang II are concerned, have been used in the present study to elucidate Ang II regulation of CA by determining its cellular action on the norepinephrine transporter (NET) system. Ang II causes both acute and chronic stimulation of [3H]-norepinephrine (NE) uptake in neuronal cultures of Wistar Kyoto (WKY) rat brain. Acute stimulation begins as early as 5 min, reaches maximal levels in about 30 min in the presence of 100 nM Ang II, and is blocked by losartan, a specific antagonist for AT1 receptor subtype. In addition, this acute stimulation appears to be a posttranscriptional event and does not involve protein kinase C (PKC) or NET gene transcription. Chronic stimulation of [3H]-NE uptake by Ang II persists throughout the duration of Ang II incubation (24 h), is dose dependent, and is also mediated by AT1 receptor subtype. However, chronic stimulation of [3H]-NE uptake involves PKC, cfos, and NET gene transcription. Ang II also stimulates [3H]-NE uptake in neuronal cultures of SH rat brain, both acutely and chronically, by mechanisms similar to those observed in neuronal cultures of WKY rat brain. The stimulation of NET by Ang II is 2-fold higher than that seen in WKY and is consistent with increased AT1 receptor gene transcription and increased functional AT1 receptors in SH rat brain neurons compared with WKY rat brain neurons. The Ang II stimulation of the NET system is also higher in adult SH compared with WKY rats in vivo. These observations show that 1) Ang II stimulates the NET system both acutely and chronically, the former involving activation of preexisting transporters and the latter involving NET gene transcription and translation; and 2) Ang II stimulation of the NET system is elevated in SH rat brain neurons.

Angiotensin II↗
PubMed1996

Angiotensin II regulation of tyrosine hydroxylase gene expression in the neuronal cultures of normotensive and spontaneously hypertensive rats.

In the present study we investigated the regulation of tyrosine hydroxylase (TH) by angiotensin II (Ang II) in an attempt to provide cellular and molecular evidence that this hormone has increased neuromodulatory actions in the spontaneously hypertensive (SH) rat brain. Neuronal cells in primary culture from the hypothalamus-brain stem of both normotensive [Wistar-Kyoto (WKY)] and SH rats have been used. These cultures mimic in vivo situations. Ang II caused a time-dependent increase in TH activity in WKY rat brain neurons. A maximal increase of 2.5-fold was observed with 100 nM Ang II in an actinomycin- and cycloheximide-dependent process. In addition, Ang II caused a parallel increase in TH messenger RNA (mRNA) levels, with a maximal stimulation of 5-fold in 4 h by 100 nM Ang II in WKY rat brain neurons. The stimulation of TH mRNA was mediated by the AT1 receptor subtype, resulted from an increase in its transcription, and involved activation of phospholipase C and protein kinase C. Antisense oligonucleotide for c-fos attenuated Ang II stimulation of TH mRNA in a time- and dose-dependent fashion, indicating an involvement of c-fos as a putative third messenger in Ang II stimulation of TH. Ang II also caused stimulation of TH activity and its mRNA levels in neuronal cultures of SH rat brain by a mechanism similar to that observed for neuronal cultures of WKY rat brain, involving AT1 receptors, protein kinase C, and c-fos. However, the stimulation of TH activity and that of TH mRNA were approximately 30% and 80% higher, respectively, in the SH rat brain neurons than those in the WKY rat brain neurons. In vivo experiments have been carried out to validate the elevated response of TH gene expression to Ang II in SH rat brain neuronal cultures. Ang II stimulated both TH activity and TH mRNA levels in the hypothalami and brain stems of adult WKY and SH rats. The level of stimulation in the brain of the SH rat was significantly higher than that in the WKY rat. These observations are consistent with an increase in AT1, receptor gene expression and suggest that increased TH gene expression could be the cellular/molecular basis for the greater neuromodulatory action of Ang II in the SH rat brain.

Angiotensin II↗
PubMed1995

Neuropeptide Y injection into the fourth cerebroventricle stimulates c-Fos expression in the paraventricular nucleus and other nuclei in the forebrain: effect of food consumption.

Injection of neuropeptide Y (NPY) into the cerebroventricular system of the rat results in a robust feeding response. In this study, we observed that NPY injection into the fourth ventricle augmented feeding and Fos-like immunoreactivity (FLI) in the paraventricular nucleus (PVN) and in other neighboring nuclei in the forebrain previously implicated in stimulation of feeding. Since the rostral transport of NPY in cerebrospinal fluid after injection into the fourth ventricle is unlikely and the topography of FLI as well as feeding behavior seen in this study are similar to those observed previously after NPY injection into the lateral cerebroventricle, these findings are in accord with the view that feeding induced by NPY injection into the fourth ventricle may also be mediated by NPY receptive elements in the forebrain.

Analysis of Variance↗
PubMed1995

Sodium depletion and Fos-immunoreactivity in lamina terminalis.

Rats were either depleted of sodium by treatment with a diuretic or were made hypovolemic by injection of polyethylene glycol (PEG) and their brains were subsequently examined for induction of Fos-like immunoreactivity (FLI). FLI was observed in the lamina terminalis (LT) after both treatments; FLI was observed in the magnocellular neurosecretory hypothalamic areas only after PEG. Implications of these data for brain substrates of sodium appetite are discussed.

Animals↗
PubMed1995

Pregastric and postabsorptive inhibitory effects of water on angiotensin-induced Fos in rat brain.

Intraventricularly (ICV)-injected Ang II activates cells in several forebrain structures of rats, including SFO, OVLT, PVN and SON, and produces a spectrum of physiological and behavioral responses. It has been reported that the Fos-like immunoreactivity (FLI; a marker of cell activation) that is induced in PVN and SON by exogenous Ang II is prevented by allowing rats to ingest water after injection. The present study tests whether this inhibitory effect of water is due to either preabsorptive (oral) or postingestive factors, or both. Rats received cerebroventricular injection of Ang II (100 ng) and were killed 1 h later. One group received no water after the injection, another group drank water, a third group drank water but had it drain from a gastric fistula (sham drinking), and a fourth group received an intragastric infusion of water. In confirmation of a previous study, rats allowed to drink water after Ang II showed an almost complete absence of FLI in SON and PVN, compared with those not allowed access to water. Both sham drinking and intragastrically-infused rats showed less FLI in SON and PVN than nondrinkers. The reduction was greater in the infused group than the sham drinkers, but was not as great as in those allowed to drink water and absorb it. This suggests that both orally-mediated as well as postabsorptive factors can inhibit Ang II-induced FLI by impinging upon cells in the SON and PVN. In contrast, Ang II-induced FLI in OVLT and SFO was not affected by any of the oral or gastric water conditions.

Angiotensin II↗
PubMed1995

Neural activity and meal-associated drinking in rats.

Rats were allowed to eat a meal (chow or cracker) of approximately normal spontaneous size either with or without water available. They were then sacrificed for measurement of either plasma renin activity (PRA) and gut contents at the end of the meal or Fos-immunoreactivity (FLI) in brain 1 h after the meal. PRA was doubled at the end of the meal relative to unfed controls, and this coincided with translocation of fluid into the gut. The supraoptic and magnocellular paraventricular nuclei showed meal-related FLI. The intensity of the FLI was related to meal size, and was less prominent in rats eating moist food. This study shows that normal-sized meals produce detectable changes in fluid parameters and activate brain locations known to be related to primary stimuli of drinking.

Angiotensin II↗
PubMed1995

Fos induced in brain of spontaneously hypertensive rats by angiotensin II and co-localization with AT-1 receptors.

The induction of Fos-like immunoreactivity (FLI) by peripheral administration of angiotensin II (Ang II) was used to determine whether central activation was greater in spontaneously hypertensive rats (SHR) than in normotensive WKY and outbred Wistar controls. FLI was induced in the same brain regions (circumventricular organs and neurosecretory hypothalamic cell groups) in all three groups of rats, but the FLI in several of these regions was markedly less in WKY than in either SHR or Wistar. This reduced responsiveness in supraoptic and paraventricular nuclei was selective to Ang II, because the FLI induced in these nuclei by hypertonic NaCl did not differ between groups. We also report that a considerable number of cells in the SON and PVH expressing FLI to these stimuli show immunostaining with an antibody to the AT-1 Ang II receptor. These data indicate that central angiotensinergic pathways may be more sensitive in SHR than WKY, and that WKY are less sensitive than outbred Wistars.

Angiotensin I↗
PubMed1995

Bradykinin-induced water intake and brain fos-like immunoreactivity in rats.

We have previously shown that peripheral injection of bradykinin in combination with the kininase II inhibitor, captopril, to rats produces a robust water intake. We now extend this observation to another kininase II inhibitor, enalapril. Water intake increases with dose of dose of bradykinin, but has an inverted U-shaped relationship with dose of kininase II inhibitor. The induced water intake is completely blocked by peripheral administration of the bradykinin antagonist, Hoe 140, and is partly attenuated by peripheral injection of an angiotensin (Ang) II receptor antagonist, losartan. Relative to captopril alone, the combination of captopril and bradykinin greatly elevated plasma renin activity, but did not reduce blood pressure. We further show that, while either bradykinin or enalapril alone induce little or no Fos-like immunoreactivity in areas of the brain related to fluid balance, their combination induces staining in many cells in the supraoptic and paraventricular magnocellular nuclei, as well as along the lamina terminalis. These data suggest that bradykinin may have a role in regulation of fluid balance, partly mediated through Ang II.

Angiotensin I↗
PubMed1995

Preference for NaCl solutions in sham drinking Sprague-Dawley rats: water deprivation, sodium depletion, and angiotensin II.

Male Sprague-Dawley rats were fitted with closable gastric fistulas and were then tested under closed fistula (real intake) and open fistula (sham intake--fluids drain from the stomach without appreciable absorption) conditions in one of three states: fluid deprivation, sodium depletion, and infusion of angiotensin (Ang) II. Water and various concentrations of NaCl were offered to drink in 1-h one- or two-bottle intake tests. In Experiment 1, water-deprived rats with closed fistulas drank more 0.15 M NaCl than either water or 0.3 M NaCl, offered in one-bottle tests. In sham drinking tests, the intake decreased monotonically as NaCl concentration increased. In two-bottle tests, water was greatly preferred over NaCl solutions. In Experiment 2, sodium-depleted rats preferred NaCl over water, again demonstrating a peak intake at 0.15 M in closed fistula conditions. However, with the fistula open the intakes of 0.05 and 0.15 M were similar, and 0.45 M considerably lower. In Experiment 3, Ang II-infused rats consumed both water and NaCl in two-bottle tests in both open and closed fistula trials. The quantity ingested on sham trials was only modestly elevated over real intake trials with Ang II compared with sham tests in Experiments 1 and 2.

Angiotensin II↗
PubMed1995

Effect of dexfenfluramine on metabolic and neurochemical measures in restraint-stressed ob/ob mice.

Genetically obese (ob/ob) and lean C57BL/6J mice were subjected to 1 h acute restraint stress, and the effects on plasma glucose and corticosterone, and brain amines, were assessed relative to nonrestrained groups. Some mice were treated with dexfenfluramine (DFEN) prior to restraint. Compared with their lean counterparts, ob/ob mice had elevated basal plasma levels of both glucose and corticosterone. Both lean and ob/ob showed comparable absolute restraint-induced increments in these measures, but the fractional increase was much smaller in ob/ob. Metabolism of NE, DA and 5-HT was also assessed from the ratio of the metabolite-to-amine in various brain regions. Obese mice had smaller restraint-related increases in monoamine metabolism than lean their counterparts. Acute DFEN increased corticosterone, but tended to reduce the restraint-induced elevations in glucose and monoamine metabolism.

Animals↗
PubMed1995

Effect of administration of angiotensin II and isoproterenol, alone and in combination, on drinking and tail skin temperature of the rat.

Both angiotensin II (AII) and the beta-adrenergic agonist isoproterenol are well known to induce drinking and increase tail skin temperature (TSK) in rats. Previous studies have shown that these two compounds have an additive, rather than interactive, dipsogenic effect when administered together. The present studies confirmed the additivity of the dipsogenic effect of the two compounds and attempted to extend these results to TSK. The results reveal that at a series of dosage combinations of AII [100 and 125 micrograms/kg, subcutaneously (SC)] and isoproterenol (ISOP) (10, 12.5, and 25 micrograms/kg, SC) administered together, the increase in TSK usually induced by each compound was canceled. This occurred at the lower doses of ISOP in combination with AII. Thus, the differences between dipsogenic and thermoregulatory effects of combined doses of AII and ISOP suggest a difference in central integration. Important differences between the thermoregulatory responses to administration of the two compounds include increases in metabolic rate and colonic temperature when ISOP is administered and decreases in both when AII is administered. It is suggested that the effect of the two compounds to cancel each other with respect to TSK is related to their opposite effects on metabolic rate.

Angiotensin II↗
PubMed1995

Effects of vagotomy on cholecystokinin- and dexfenfluramine-induced Fos-like immunoreactivity in the rat brain.

This study compared the effects of bilateral subdiaphragmatic vagotomy on the Fos-like immunoreactivity (FLI), a marker of neuronal activation, in rat brain induced by two anorectic agents, cholecystokinin (CCK) and the serotonin agonist, dexfenfluramine (DFEN). In the nonvagotomized rats, both CCK (5 micrograms/kg, IP) and DFEN (2 mg/kg, IP) induced FLI in the nucleus of the solitary tract (NST), the external subdivision of the lateral parabrachial nuclei (LPBE), the lateral subdivision of the central amygdaloid nucleus (CeL), and the bed nucleus of the stria terminalis (BST). However, subregional distribution of the FLI induced by the two agents was different in most of these regions. Additionally, the area postrema and the medial subdivision of the hypothalamic paraventricular nucleus were preferentially activated by CCK but not DFEN, while the caudate-putamen was activated by DFEN but not CCK. Bilateral subdiaphragmatic vagotomy completely abolished CCK-induced FLI in all the brain regions but did not attenuate DFEN-induced FLI in any of these regions, including the NST. The results of the present study suggest that DFEN-activation of the NST-LPBE-CeL/BST neuraxis is not mediated by the vagus nerve. On the other hand, and consistent with a variety of other data, activation of various parts of the brain by peripherally administered CCK depends on a vagal pathway. These data are discussed in relation to a previously proposed interaction between CCK and serotonin in mediating satiety.

Animals↗