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Biomedical subjects

N E Rowland

Publications and source records attributed to N E Rowland.

At least 37 records · Page 2Linked to original sources
PubMed1998

Central injection in rats of alpha-melanocyte-stimulating hormone analog: effects on food intake and brain Fos.

Lateral cerebroventricular (LCVT) administration of the alpha-MSH agonist analog Nle4DPhe7alpha-MSH (NDP-MSH) inhibited food intake in food-deprived rats, but did not inhibit water intake in water-deprived rats. When NDP-MSH was administered into the fourth ventricle (4CVT), comparable suppressions of food intake were observed. LCVT and 4CVT administration of NDP-MSH also reduced spontaneous 24 h food intake. LCVT injection of NDP-MSH greatly attenuated food intake stimulated in sated rats by acute CVT administration of neuropeptide Y (NPY). These and other data suggest that alpha-MSH is an important endogenous regulator of food intake, possibly acting downstream of NPY. In an attempt to assess further the sites of action of NDP-MSH, a qualitative mapping study of Fos-like immunoreactive (Fos-ir) neurons was performed following LCVT administration of NDP-MSH. LCVT injection of NDP-MSH induced Fos-ir in several forebrain regions including cortex, striatum, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus and arcuate nucleus. The combination of NPY and NDP-MSH did not produce obvious antagonism or cancellation of effects in any region examined. Thus, the site(s) of action of NDP-MSH on food intake remain to be clarified.

Animals↗
PubMed1998

Effects of L-arginine on angiotensin II-related water and salt intakes.

Nitric oxide (NO) has been implicated centrally as an inhibitory neuromodulator, acting in short feedback loops. Neurons capable of NO synthesis have been localized in various thirst-related hypothalamic nuclei. Intracerebroventricular (icv) injection of L-arginine (L-arg), the precursor for NO, has previously been shown to attenuate both dehydration- and angiotensin II (Ang II)-induced drinking behavior. The present study further examines the effects of L-arg on drinking. We confirmed that icv administration of L-arg (50 microg) reduced water intakes induced by both 24 h water deprivation and icv Ang II (250 ng). We additionally showed that L-arg inhibited the water intake induced by peripheral injection of Ang II and the intake of 0.3 M NaCl following 24 h sodium depletion. We demonstrated the behavioral specificity of L-arg treatment by showing that it did not inhibit the intake of sucrose in food deprived rats and did not act as an unconditional stimulus for the formation of a conditioned taste aversion. These results lend further support to the idea that NO plays a role in modulating fluid balance and drinking behavior.

Angiotensin II↗
PubMed1998

Efficacy of administration of dexfenfluramine and phentermine, alone and in combination, on ingestive behavior and body weight in rats.

Recently, a combination of the anorectics fenfluramine (FEN) and phentermine (PHEN) has been used to treat obesity. While each of these agents has been investigated in animals, little is known concerning the effects of the combination on ingestive behavior and body weight. In the present experiments, we report: (1) the effects of acute administration of dexfenfluramine (DFEN) and PHEN individually and in combination on sweetened milk intake and body weight in non-deprived rats and (2) the effects of chronic administration (7 day minipump) of DFEN, PHEN, and their combination on daily food intake and body weight both during and after the treatment period. Additionally, the effects of the 5-HT2C agonist 1-[3-(trifluoromethyl)-phenyl]piperazine (TFMPP) alone and in combination with PHEN on food intake and body weight were assessed. Both acute and chronic administration of DFEN and PHEN revealed that in combination they are more effective than when given individually. However, the DFEN/ PHEN combination does not appear to exert effects that are selective for food intake because water intake was markedly suppressed in water-deprived rats. PHEN alone or in combination with either DFEN or TFMPP also produced increased activity or alertness during the day when controls normally were asleep. While anorectic combinations such as DFEN/PHEN may be effective at promoting weight loss and reducing food intake, future studies on their specificity, safety and efficacy are warranted.

Animals↗
PubMed1998

NaCl appetite in two strains of rat reported to be resistant to mineralocorticoid-induced hypertension.

Both Long-Evans (LE) and Wistar-Furth (WF) strains of rat are known to be resistant to development of hypertension by mineralocorticoid (MC) treatment. MC-induced hypertension is, in part, mediated by the brain. We have examined another aspect of central MC action, the induction of NaCl appetite in these strains, by using the more common Sprague-Dawley (SD) and Wistar (WS) strains for comparison. In the first experiment, LE and SD rats were administered three treatments known to induce an appetite for NaCl solution in rats. Administration of deoxycorticosterone acetate (DOCA) increased the intake of 0.45 M NaCl in both strains, but the amounts consumed were about 2-fold greater in LE rats than in SD rats. Administration of captopril also increased NaCl intake, but there were no differences between LE and SD rats. NaCl depletion with furosemide induced NaCl appetite in both strains, but the amounts consumed were about 2-fold greater in LE rats than in SD rats. In the second experiment, adult male WF and WS rats were administered DOCA, enalapril, or furosemide and NaCl appetite was determined. Both strains showed comparable NaCl appetite during each of these treatments. However, during a 5-week regimen of DOCA with only NaCl-KCl solution to drink, uninephrectomized WF rats consumed less than WS rats. Thus, despite reported resistance to MC-induced hypertension, neither LE nor WF strains of rats showed correspondingly marked deficits in induced NaCl appetite.

Analysis of Variance↗
PubMed1998

Brain mechanisms of mammalian fluid homeostasis: insights from use of immediate early gene mapping.

A comprehensive review of the literature through mid-1997 is presented on the application of immediate early gene mapping to problems related to brain mechanisms of fluid homeostasis and cardiovascular regulation in mammals. First, the basic mechanisms of fluid intake and the principles and pitfalls of immediate early gene mapping are briefly introduced. Then, data from several principal paradigms are reviewed. These include fluid deprivation and intracellular dehydration, both of which are associated with thirst and water intake. The contributions of peripheral sodium receptors, and of both hindbrain and forebrain integrative mechanisms are evaluated. Extracellular dehydration, and associated aspects of both thirst and sodium appetite are then reviewed. The contributions of both structures along the lamina terminalis and the hypothalamic magnocellular neurosecretory groups figure prominently in most of these paradigms. Effects of hypotension and hypertension are discussed, including data from the endogenous generation and the exogenous application of angiotensin II. Lastly, we summarize the contribution of the early gene mapping technique and consider briefly the prospects for new advances using this method.

Animals↗
PubMed1997

Comparison of Fos induced in rat brain by GLP-1 and amylin.

The patterns of Fos-like immunoreactivity (Fos-ir) in rat brain were compared following treatment of rats with two anorectic 'gut' peptides. Central administration of GLP-1 produced dose-related increases in Fos-ir in the area postrema (AP) and caudal nucleus of the solitary tract (cNTS) as well as strong activation in the lateral parabrachial nucleus (LPBE), hypothalamic paraventricular nucleus (PVN), bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA). At centrally-active doses, peripheral administration of GLP-1 did not induce Fos-ir in brain. In contrast, peripheral administration of amylin produced strong Fos-ir in the AP and cNTS, as well as the BNST and CeA, but not in the PVN. The common activation of the LPB-BNST-CeA by these and other previously-studied anorectics suggest this is an important circuit involved in satiety.

Amyloid↗
PubMed1997

Effect of chronic treatment with propranolol on the cardiovascular responses to chronic cold exposure.

The purpose of this study was to determine whether beta-adrenergic receptors are involved in the elevation of blood pressure, tachycardia, and cardiac hypertrophy in rats chronically exposed to cold (5 degrees C). Four groups of rats were used. Two groups of rats were exposed to 5 degrees C and the other 2 groups were kept at 25 degrees C. In each temperature condition, one group received regular food while the other received food to which a nonspecific beta-adrenoceptor antagonist, d,l-propranolol, was added. The blood pressure of the untreated, cold-exposed group increased significantly within 3 weeks of exposure to cold and remained elevated until the end of the experiment. Chronic treatment with d,l-propranolol decreased the rate of cold-induced elevation of blood pressure at doses of 1.0 and 1.2 g/kg of food, and produced a complete reversal of hypertension at a higher dose ( 1.5 g/kg of food). Propranolol also prevented tachycardia in cold-exposed rats. The fact that propranolol decreased the elevation of blood pressure and prevented tachycardia suggests that both beta1- and beta2-adrenoceptors are blocked in cold-exposed rats. Propranolol, however, did not affect cold-induced cardiac hypertrophy.

Adrenergic beta-Antagonists↗
PubMed1997

Role of angiotensin in the dipsogenic effect of bradykinin in rats.

We have previously shown that peripheral administration of bradykinin (BK) induces water intake in rats acutely pretreated with captopril, a kininase II inhibitor. We now show that BK-induced drinking is also observed in rats treated chronically with dietary captopril, and that this is reversed by Hoe 140, a BK receptor antagonist. Both acute and chronic captopril in combination with BK caused a large increase in plasma renin activity. Fos-like immunoreactivity (Fos-in used as a marker of cellular activation) was induced by BK + captopril in regions of the brain previously associated with action of angiotensin (Ang) II, including the circumventricular organs and the magnocellular hypothalamic nuclei. However, while water intake induced by peripheral administration of Ang I was potentiated by acute administration of captopril, it was suppressed by chronic captopril treatment. Fos-IR induced in brain by Ang I was not markedly affected by either acute or chronic treatment with captopril. The simultaneous occurrence of potentiated drinking to BK and inhibited drinking to Ang I following chronic treatment with captopril suggest that different mechanisms of action are involved. In order to further examine this possibility, rats were given lesions of the anterodorsal third ventricle region. Lesions that completely abolished the water intake following administration of Ang II only partly attenuated water intake induced by BK + captopril. Further, Fos-IR induced by BK + captopril was only partly (31%) reduced in the supraoptic and paraventricular nuclei of lesioned rats compared with sham operated controls. We suggest that at least two mechanisms, one Ang-related, underlie drinking after BK+captopril.

Angiotensin I↗
PubMed1997

Aging and fluid homeostasis in rats.

The capacity of aging rats to defend body fluid homeostasis in response to a variety of dipsogenic and natriorexigenic stimuli was assessed. Male and female rats of both the Fischer 344 (FR) and Sprague-Dawley (SD) strains were used and tested at target ages of approximately 5, 10, 15, and 20 mo in both longitudinal and cross-sectional studies. There were no consistent age-related declines in water intake in response to water deprivation or acute administration of hypertonic NaCl; angiotensin (ANG) I, II, III; or isoproterenol. Likewise, there were no major impairments in either urinary excretion of the hypertonic NaCl load or excretion of water or hypotonic NaCl loads, although the latter were excreted more slowly in the older cohorts. The preference/aversion functions for NaCl solutions differed between SD and FR rats, but did not change with age except in male FR rats that lost their aversion to dilute NaCl at 20 mo of age. Intake of hypotonic NaCl solution after acute sodium depletion (furosemide treatment) showed a partial decline with age, and the older rats sustained larger estimated sodium deficits after a 6-h repletion period. A more complete age-related decline was observed in the intake of hypertonic NaCl stimulated by chronic dietary administration of a kininase II inhibitor (ramipril). Male rats of 15-20 mo of age showed no ramipril-induced sodium appetite. Brain ANG II receptor density, determined by autoradiography, declined by almost 50% in the paraventricular nucleus at 20 mo of age and declined slightly in the organum vasculosum laminae terminalis but did not decline in either the supraoptic nucleus or subfornical organ. Thus the major deficits in fluid intake in aging rats are related to salt appetite; the mechanism was not identified definitively.

Aging↗
PubMed1996

Losartan inhibition of angiotensin-related drinking and Fos immunoreactivity in hypertensive and hypotensive contexts.

We assessed the ability of acute peripheral administration of the AT-1 receptor antagonist, losartan, to reverse both the water intake and Fos-immunoreactivity (Fos-ir) induced in rats by either peripheral or cerebroventricular (i.c.v.) administration of angiotensin (Ang) II. We compared this with endogenous generation of Ang II during either hypovolemia or hypotension. Relatively low doses of losartan blocked the dipsogenic effect of peripherally administered exogenous Ang II, but a higher dose (20 mg/kg) was needed to block the dipsogenic effect of i.c.v.-administered Ang II. Fos-ir induced by i.c.v. Ang II was attenuated in SFO and SON by 10-20 mg losartan/kg given peripherally, but Fos-ir in the MnPO and PVN was unaffected. These findings suggest that losartan has limited permeability into the brain. We used peripheral losartan to assess the contribution of Ang II to water intake and Fos-ir responses to peripheral injection of either polyethylene glycol (PEG; a colloid that produces non-hypotensive hypovolemia) or isoproterenol (hypotensive agent). Water intakes were unaffected by the higher dose of losartan given s.c. Intraperitoneal injection of EXP 3174, the active metabolite of losartan that may more readily penetrate the blood-brain barrier, inhibited isoproterenol-, but not PEG-induced water intakes. Fos-ir was induced by PEG and isoproterenol in several regions of the brain also activated by Ang II. Fos-ir was greatly attenuated in the SFO by losartan following administration of PEG, but not isoproterenol, and was either unaffected or increased in SON and PVN after either agent. These data suggest that the increased circulating Ang II following PEG or isoproterenol acts at the SFO and is more readily reversible by losartan in normotensive (PEG) than in hypotensive (isoproterenol) states. Non-Ang neural input to the SON and PVN, presumably from baroreceptors, appears to be sufficient to produce strong Fos-ir in these regions, as well as to engage drinking.

Angiotensin II↗
PubMed1996

Age-related decline in thirst and sodium appetite in rats related to kininase II inhibition.

Water intake was examined in young (3-5 months) and old (20-24 months) rats following peripheral administration of either angiotensin (Ang) II or captopril+bradykinin (BK). Relative to body weight, intake after Ang II showed no age-related difference, while that after captopril+BK was markedly reduced in the old rats. In other rats that were not allowed to drink after captopril+BK, the induction of Fos-like immunoreactivity (IR) was much lower in the subfornical organ, supraoptic and median preoptic nuclei of old rats compared with their young counterparts. Intake of 0.15 M NaCl during chronic dietary administration of enalapril was robust in young rats but was much reduced in old rats, as was their plasma renin activity. Thus, reduced thirst and sodium appetite are found in conjunction with kininase II (angiotensin-converting enzyme) inhibitors in aging rats, possibly because they fail to generate the high levels of circulating renin seen in young rats under these conditions.

Aging↗
PubMed1996

Angiotensin-related induction of immediate early genes in rat brain.

Several studies are reviewed in which behavioral aspects of angiotensin (Ang) II on fluid intake have been compared with induction of the immediate early gene product, Fos, as a marker of neuronal activation in rat bain. Either peripheral or central administration of Ang II induced Fos along the lamina terminalis (SFO, MnPO, AV3V) and in the magnocellular neurosecretory groups (SO, PVH). A similar pattern is seen with central injection of renin. Both pharmacological and antisense oligonucleotide probe studies indicate that an AT1 receptor is involved, probably with the initial transduction in the SFO. Treatments that induce sodium appetite all induce Fos along the lamina terminalis, but usually not in the SO or PVN. Kininase II inhibitors, such as captopril, acutely potentiate drinking to Ang I, but after chronic exposure they may inhibit water intake. In contrast, the dipsogenic effect of bradykinin which is manifest in the presence of acute captopril remains unaffected by chronic administration. This suggests that the sodium appetite that appears with chronic captopril treatment may depend in part on peptides other than Ang.

Angiotensin II↗
PubMed1996

Effects of dexfenfluramine or 5,7-dihydroxytryptamine on tryptophan hydroxylase and serotonin transporter mRNAS in rat dorsal raphe.

Dexfenfluramine (DF), given in high doses, can produce long-lasting decreases in brain levels of serotonin (5-HT) and 5-HT transporter (5-HTT) protein. The purpose of this study was to determine if DF-induced decreases in 5-HT and 5-HTT in rat forebrain are correlated with compensatory changes in the expression of the genes for tryptophan hydroxylase (TPH) and 5-HTT in the dorsal raphe nucleus. Gene transcripts were measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Rats were treated with either one or eight injections of DF at either high (10 mg/kg) or low (2 mg/kg) doses. A positive control group for 5-HT cell loss received a single cerebroventricular injection of 5,7-dihydroxytryptamine (DHT). Rats were killed either 5, 15 or 30 days after their last treatment. Paroxetine binding to the 5-HTT protein in frontal cortex was, as expected, reduced in all of the treated groups relative to vehicle controls. TPH mRNA levels in the dorsal raphe of animals that received DHT were significantly higher than those measured in all other treatment groups 15 days following treatment. By 30 days, the amount of TPH mRNA in DHT-treated rats had fallen to well below control levels. None of the DF regimens significantly affected TPH mRNA levels. Unlike the TPH mRNA changes in DHT-treated rats, the 5-HTT mRNA levels in the dorsal raphe declined progressively throughout the 30 day survival period. None of the DF regimens significantly affected 5-HTT mRNA levels. The significance of these data are discussed in terms of whether loss of forebrain markers for 5-HT reflects either the loss of fine caliber 5-HT axon terminals or a decrease in the expression of these markers in the somata of these cells which are located in the dorsal raphe.

5,7-Dihydroxytryptamine↗
PubMed1996

Effect of chronic dexfenfluramine on Fos in rat brain.

The acute appetite suppressant effect of dexfenfluramine (DF) in rats, which may depend upon its action to release serotonin (5-HT) in the brain, often declines with repeated dosing (tolerance). The mechanisms of this tolerance remain unclear. Previously, we used Fos-like immunoreactivity (Fos-IR) to map potential brain sites activated by single injections of DF in rats. A dose of 5 mg DF/kg activated the central amygdala (CeA), bed nucleus of the stria terminalis (BST), caudate-putamen (CPu), lateral parabrachial nucleus (LPB), nucleus tractus solitarius (NST), frontal cerebral cortex and the parvocellular paraventricular hypothalamic nucleus (PVN). We now report studies using Fos-IR in an attempt to understand which regions might underlie tolerance to the action of DF. Pretreatment of rats with an escalating dosage regimen of DF (0.5-4 mg/kg, i.p.) was associated with complete loss of Fos-IR to a probe dose (5 mg DF/kg) in the cortex, CPu, PVN and NTS, and partial loss of Fos-IR in the BST, CeA and LPB. Second, repeated treatment with DF (2 mg/kg), which has been shown to produce tolerance the anorexia caused by DF but not cholecystokinin (CCK), likewise reduced Fos-IR induced in the above brain regions, but had no effect on Fos-IR induced by either CCK or the 5-HT agonist, 5-carboxamidotryptamine. Third, repeated treatment with 5-HT (2 mg/kg, s.c.) had no effect on Fos-IR induced by a probe dose of DF. These data show that regionally heterogeneous hyporesponsiveness to the induction of Fos by DF develops after repeated low doses of DF; however, the Fos response to other putative anorectics or weight reducing agents is not affected. This may be related to behavioral tolerance.

Animals↗
PubMed1996

Expression of Fos in rat brain in relation to sodium appetite: furosemide and cerebroventricular renin.

Two experiments were performed to investigate the relationship between the expression of sodium appetite and the appearance of Fos-like immunoreactivity (Fos-IR) in the brain of rats. In the first experiment, rats were depleted of sodium by treatment with furosemide 24 h prior to sacrifice and without access to either food or sodium solution. Some rats had access to distilled water, and others had no fluids available during the 24 h. All of the furosemide-treated rats showed Fos-IR in both the subfornical organ (SFO) and around the organum vasculosum laminae terminalis (OVLT). Rats with access to distilled water during the depletion period showed no Fos-IR in the supraoptic (SON) or paraventricular hypothalamic nuclei (PVN) and, in parallel behavioral studies, comparably-treated rats consumed only 0.3 M NaCl solution at the end of the 24 h. In rats that had no fluids during the deprivation period, only about one half showed Fos-IR in SON and PVN and, in parallel behavioral studies, comparably treated rats consumed both water and 0.3 M NaCl solution at the end of 24 h. In a second experiment, cerebroventricular administration of renin stimulated short latency intake of 0.3 M NaCl and water. The relative intakes of water and NaCl were comparable at a low dose of renin, but intake of water exceeded that of NaCl after higher doses. Renin induced Fos-IR in SFO, MnPO, peri-OVLT region, SON and PVN. Both Fos-IR and fluid intake were antagonized by administration of losartan, an angiotensin II type 1 receptor antagonist. Thus, only the circumventricular organs of the lamina terminalis showed Fos-IR during each natriorexigenic regimen in these studies. These data support the view that Ang II of both central and peripheral origin activates the SFO and/or peri-OVLT region and contributes to sodium appetite.

Animals↗
PubMed1996

Peripherally and centrally administered bombesin induce Fos-like immunoreactivity in different brain regions in rats.

Bombesin (BBS) suppresses food intake when administered either peripherally or centrally to rats, but the brain systems involved in the anorectic action remain unclear. We addressed this question by examining Fos-like immunoreactivity (Fos-IR), a marker of neuronal activation, in rat brain following either intraperitoneal (i.p.) or 4th cerebroventricular (4V) administration of BBS. It was found that the hypothalamic paraventricular nucleus showed strong Fos-IR following either i.p. BBS in the dose range 20-80 micrograms/kg, or 4V BBS at a dose of 60 ng/rat. Additionally, different effects of i.p. and 4V BBS were observed in the following regions: (1) a strong Fos-IR was seen in the area postrema (caudal part) only following i.p. but not 4V BBS; (2) while i.p. BBS-induced Fos-IR was almost evenly distributed throughout the medial subdivision of the nucleus of the solitary tract, 4V BBS-induced Fos-IR was much stronger in the rostral part than in the caudal part of this region; (3) although the lateral parabrachial nucleus, the central nucleus of the amygdala and the bed nucleus of the stria terminalis showed strong Fos-IR following both i.p. and 4V BBS, subregional distribution of the Fos-IR was not the same. These sites were previously found to show strong Fos-IR after administration of either cholecystokinin (CCK) or dexfenfluramine (DF), but with different subregional distribution. The Fos-IR pattern induced by i.p. BBS was similar to that induced by CCK, and the Fos-IR pattern induced by 4V BBS was similar to that induced by DF.

Animals↗
PubMed1996

Satietin: Fos mapping of putative brain sites of action.

A purified extract of a blood-borne satiety factor, called satietin, was injected into the cerebral ventricles of rats that were either fed ad libitum or were food deprived. The animals were killed 2 h after injection and their brains subsequently sectioned and stained for Fos-like immunoreactivity (Fos-IR) to determine the putative sites of action for satietin in the brain. Fos-IR was induced in only a few locations, the most prominent sites being the bed nucleus of the stria terminalis, the central nucleus of the amygdala, and the parvocellular division of the paraventricular nucleus of the hypothalamus. Each of these areas has previously been implicated in the control of feeding behavior. Sites in the hindbrain that are associated with nausea were devoid of satietin-induced Fos-IR. Finally, these sites of action of satietin show some differences from sites that are prominently activated by other classes of anorectic agents.

Amygdala↗