Thirst and salt appetite responses in young and old Brown Norway rats

2003 ◽  
Vol 284 (2) ◽  
pp. R317-R327 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Alan Kim Johnson

Male Brown Norway rats aged 4 mo (young) and 20 mo (old) received a series of experimental challenges to body fluid homeostasis over ∼3 mo. Water was available for drinking in some tests, and both water and 0.3 M NaCl were available in others. The series included three episodes of extracellular fluid depletion (i.e., furosemide + 20 h of sodium restriction), two tests involving intracellular fluid depletion (i.e., hypertonic saline: 1 or 2 M NaCl at 2 ml/kg body wt sc), one test involving overnight food and fluid restriction, and testing with captopril adulteration of the drinking water (0.1 mg/ml) for several days. Old rats were significantly heavier than young rats throughout testing. Old rats drank less water and 0.3 M NaCl after sodium deprivation than young rats, in terms of absolute and body weight-adjusted intakes. Old rats drank only half as much water as young rats in response to subcutaneous hypertonic NaCl when intakes were adjusted for body weight. Old rats drank less 0.3 M NaCl than young rats after overnight food and fluid restriction when intakes were adjusted for body weight. In response to captopril adulteration of the drinking water, young rats significantly increased daily ingestion of 0.3 M NaCl when it was available as an alternative to water and significantly increased daily water intakes when only water was available, in terms of absolute and body weight-adjusted intakes. Old rats had no response to captopril treatment. These results add important new information to previous reports that aging rats have diminished thirst and near-absent salt appetite responses to regulatory challenges.

2009 ◽  
Vol 297 (1) ◽  
pp. R149-R157 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Terry G. Beltz ◽  
Alan Kim Johnson

Compared to young cohorts, old rats drink less water in response to several thirst-inducing stimuli. In these experiments, we characterized water drinking in response to hypotension and cellular dehydration in young (4 mo), middle-aged adult (12 mo) and old (29–30 mo) male Brown Norway rats. We injected the vasodilator, minoxidil as an intravenous bolus in a range of doses (0–20 mg/kg), so that drinking responses could be compared at equivalent reductions of arterial pressure. Old rats had greatly diminished reflex tachycardia and became significantly more hypotensive after minoxidil compared with young and middle-aged rats. When compared at equivalent reductions of arterial pressure, old rats drank one-third as much as middle-aged rats, and one-fifth as much as young rats. In addition, there were age-related deficits in drinking in response to a range of administered loads of sodium (0.15–2 M NaCl, 2 ml/100 g body wt). Urinary excretion of water and sodium in response to the loads was equivalent across ages. Both middle-aged and old rats were less able than young rats to repair their water deficits after sodium loading, attributable almost entirely to their reduced drinking responses compared with young rats. Lastly, age-related declines in drinking appeared to be more severe in response to hypotension than in response to cellular dehydration.


2014 ◽  
Vol 135 ◽  
pp. 180-188 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Terry Beltz ◽  
Alan Kim Johnson

2013 ◽  
Vol 305 (12) ◽  
pp. R1498-R1505 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Terry G. Beltz ◽  
Alan Kim Johnson

This work examined the effects of age on salt appetite measured in the form of daily saline (i.e., 0.3 M NaCl) drinking in response to administration of deoxycorticosterone acetate (DOCA; 5 mg/kg body wt) using young (4 mo), “middle-aged” adult (12 mo), and old (30 mo) male Brown Norway rats. Water and sodium intakes, excretions, and balances were determined daily. The salt appetite response was age dependent with “middle-aged” rats ingesting the most saline solution followed in order by young and then old rats. While old rats drank the least saline solution, the amounts of saline ingested still were copious and comprise an unambiguous demonstration of salt appetite in old rats. Middle-aged rats had the highest saline preference ratios of the groups under baseline conditions and throughout testing consistent with an increased avidity for sodium taste. There were age differences in renal handling of water and sodium that were consistent with a renal contribution to the greater saline intakes by middle-aged rats. There was evidence of impaired renal function in old rats, but this did not account for the reduced saline intakes of the oldest rats.


2020 ◽  
Author(s):  
Dorota L. Stankowska ◽  
Wei Zhang ◽  
Shaoqing He ◽  
Vignesh R. Krishnamoorthy ◽  
Payton Harris ◽  
...  

AbstractPurposeTo determine if dietary administration of the dual ETA/ ETB receptor antagonist, macitentan, could protect retinal ganglion cells (RGCs) following endothelin-1 (ET-1) mediated vasoconstriction in Brown Norway rats.MethodsAdult male and female Brown Norway rats were either untreated or treated with macitentan (5 mg/kg body weight) once a day for 3 days followed by intravitreal injection of either 4 μl of 500 μM ET-1 (2 nmole/eye) or vehicle in one eye. Imaging of the retinal vasculature using fluorescein angiography was carried out at various time points, including, 5, 10, 15, 25 and 30 minutes. Following the imaging of the vasculature, rats were either treated with macitentan (5 mg/kg/body weight in dietary gels) or untreated (control gels without medication). Following treatments, rats were euthanized, retinal flat mounts were prepared, immunostained for RGC marker Brn3a, imaged and surviving RGCs were counted in a masked manner.ResultsVasoconstrictive effects following intravitreal ET-1 injection were greatly reduced in rats administered with macitentan in the diet prior to the ET-1 administration. ET-1 intravitreal injection produced a 31% loss of RGCs which was significantly reduced in macitentan-treated rats. Following ET-1 administration, GFAP immunostaining was increased in the ganglion cell layer as well as in the retrolaminar region, suggestive of astrocytic activation by ET-1 administration. RGC numbers in macitentan treated and ET-1 injected rats were similar to that observed in control retinas.ConclusionsET-1-mediated neurodegeneration could occur through both vascular and cellular mechanisms. The endothelin receptor antagonist, macitentan, has neuroprotective effects in retinas of Brown Norway rats that occurs through different mechanisms, including, enhancement of RGC survival and reduction ET-1 mediated vasoconstriction.


2002 ◽  
Vol 93 (1) ◽  
pp. 242-250 ◽  
Author(s):  
James A. Carson ◽  
Won Jun Lee ◽  
Joseph McClung ◽  
Gregory A. Hand

Skeletal muscle is a target of anabolic steroid action; however, anabolic steroid's affect on aged skeletal muscle is not well understood. The effect of 4 wk of nandrolone decanoate (ND) administration on hindlimb muscles of 5- and 25-mo-old Fischer 344/Brown Norway rats was examined. ND (6 mg/kg body wt) was injected every 7th day for 4 wk. Controls received an oil injection. ND significantly reduced 25-mo-old rat perirenal fat pad mass by 30%. Soleus (Sol) and plantaris (Plan) muscle-to-body weight ratios were reduced in 25-mo-old rats. ND did not affect Sol or Plan muscle-to-body weight ratios at either age. Sol DNA concentration was reduced by 25% in 25-mo-old rats, and ND increased it to 12% greater than 5-mo-old rats. ND did not affect Plan DNA content. Sol androgen receptor (AR) protein in 25-mo-old rats was reduced to 35% of 5-mo-old values. ND increased AR protein by 900% in 25-mo-old rat Sol. Plan AR concentration was not affected by aging but was induced by ND in both age groups. Aging or ND treatment did not affect glucocorticoid receptor levels in either muscle. These data demonstrate that fast- and slow-twitch rat hindlimb muscles differ in their response to aging and ND therapy.


2004 ◽  
Vol 97 (3) ◽  
pp. 1082-1090 ◽  
Author(s):  
Jason C. Gallegly ◽  
Nicole A. Turesky ◽  
Beau A. Strotman ◽  
Cathy M. Gurley ◽  
Charlotte A. Peterson ◽  
...  

Muscle mass is decreased with advancing age, likely due to altered regulation of muscle fiber size. This study was designed to investigate cellular mechanisms contributing to this process. Analysis of male Fischer 344 X Brown Norway rats at 6, 20, and 32 mo of age demonstrated that, even though significant atrophy had occurred in soleus muscle by old age, myofiber nuclear number did not change, resulting in a decreased myonuclear domain. Also, the number of centrally located nuclei was significantly elevated in soleus muscle of 32-mo-old rats, correlating with an increase in gene expression of MyoD and myogenin. Whereas total 5′-bromo-2′deoxyuridine (BrdU)-positive nuclei were decreased at older ages, BrdU-positive myofiber nuclei were increased. These results suggest that, with age, loss of muscle mass is accompanied by increased myofiber nuclear density that involves fusion of proliferative satellite cells, resembling ongoing regeneration. Interestingly, centrally located myofiber nuclei were not BrdU labeled. Rats were subjected to hindlimb suspension (HS) for 7 or 14 days and intermittent reloading during HS for 1 h each day (IR) to investigate how aging affects the response of soleus muscle to disuse and an atrophy-reducing intervention. After 14 days of HS, soleus muscle size was decreased to a similar extent at all three ages. However, myofiber nuclear number and the total number of BrdU-positive nuclei decreased with HS only in the young rats. IR was associated with an attenuation of atrophy in soleus muscles of 6- and 20- but not 32-mo-old rats. Furthermore, IR was associated with an increase in BrdU-positive myofiber nuclei only in young rats. These data indicate that altered satellite cell function with age contributes to the impaired response of soleus muscle to an intervention that attenuates muscle atrophy in young animals during imposed disuse.


2011 ◽  
Vol 111 (4) ◽  
pp. 989-998 ◽  
Author(s):  
Daniel M. Hirai ◽  
Steven W. Copp ◽  
K. Sue Hageman ◽  
David C. Poole ◽  
Timothy I. Musch

Advanced age is associated with altered skeletal muscle hemodynamic control during the transition from rest to exercise. This study investigated the effects of aging on the functional role of nitric oxide (NO) in regulating total, inter-, and intramuscular hindlimb hemodynamic control at rest and during submaximal whole body exercise. We tested the hypothesis that NO synthase inhibition ( N G-nitro-l-arginine methyl ester, l-NAME; 10 mg/kg) would result in attenuated reductions in vascular conductance (VC) primarily in oxidative muscles in old compared with young rats. Total and regional hindlimb muscle VCs were determined via radiolabeled microspheres at rest and during treadmill running (20 m/min, 5% grade) in nine young (6–8 mo) and seven old (27–29 mo) male Fisher 344 × Brown Norway rats. At rest, l-NAME increased mean arterial pressure (MAP) significantly by ∼17% and 21% in young and old rats, respectively. During exercise, l-NAME increased MAP significantly by ∼13% and 19% in young and old rats, respectively. Compared with young rats, l-NAME administration in old rats evoked attenuated reductions in 1) total hindlimb VC during exercise (i.e., down by ∼23% in old vs. 43% in young rats; P < 0.05), and 2) VC in predominantly oxidative muscles both at rest and during exercise ( P < 0.05). Our results indicate that the dependency of highly oxidative muscles on NO-mediated vasodilation is markedly diminished, and therefore mechanisms other than NO-mediated vasodilation control the bulk of the increase in skeletal muscle VC during the transition from rest to exercise in old rats. Reduced NO contribution to vasomotor control with advanced age is associated with blood flow redistribution from highly oxidative to glycolytic muscles during exercise.


2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Robert L Thunhorst ◽  
Terry G Beltz ◽  
Alan Kim Johnson

2021 ◽  
Vol 8 ◽  
Author(s):  
Amina El Ayadi ◽  
Christian Tapking ◽  
Anesh Prasai ◽  
Victoria G. Rontoyanni ◽  
Doaa R. Abdelrahman ◽  
...  

While obesity blunts the ability of muscle to mount a protein synthetic response to an amino acid infusion in older adults, it is unclear if this insensitivity to nutrition persists long term and in response to complete foods is unknown. To address this, young (2 months old) and old (17–20 months old) Brown Norway rats were randomized to receive either chow or a 12 wk diet of calorie-dense human foods. At wk 10 drinking water was supplemented with 2% heavy water, followed 2 weeks later by a flooding dose of [2H5]-phenylalanine and an oral leucine bolus, allowing the short and long-term effects of age and diet on muscle protein synthesis rates to be determined. The experimental diet increased energy intake in both young (7.4 ± 0.9%) and old (18.2 ± 1.8%) animals (P &lt; 0.01), but only led to significant increases in body weight in the former (young: 10.2 ± 3.0% (P &lt; 0.05) and old: 3.1 ± 5.1% (NS) vs. age-matched controls). Notably, energy expenditure in response to the cafeteria diet was increased in old animals only (chow: 5.1 ± 0.4; cafe: 8.2 ± 1.6 kcal.kg b.w−1.h−1; P &lt; 0.05). Gastrocnemius protein fractional synthetic rates in response to either an acute leucine bolus or two weeks of feeding were equivalent across groups irrespective of age or diet. Rodents in old age appear capable of preventing weight gain in response to a calorie-dense diet by increasing energy expenditure while maintaining the anabolic sensitivity of muscle to nutrition; the mechanisms of which could have important implications for the aging obese human.


2015 ◽  
Vol 308 (10) ◽  
pp. R807-R815 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Baojian Xue ◽  
Terry G. Beltz ◽  
Alan Kim Johnson

This work examined the effects of age on daily water and sodium ingestion and cardiovascular responses to chronic administration of the mineralocorticoid, aldosterone (ALDO) either alone or together with the glucocorticoid, dexamethasone (DEX). Young (4 mo), adult (12 mo), and aged (30 mo) male Brown Norway rats were prepared for continuous telemetry recording of blood pressure (BP) and heart rate (HR). Baseline water and sodium (i.e., 0.3 M NaCl) intake, BP, and HR were established for 10 days. Then ALDO (60 μg/day sc) was infused alone, or together with DEX (2.5 or 20 μg/day sc), for another 10 days. Compared with baseline levels, ALDO stimulated comparable increases in daily saline intake at all ages. ALDO together with the higher dose of DEX (i.e., ALDO/DEX20) increased daily saline intake more than did ALDO, but less so in aged rats. Infusion of ALDO/DEX20 increased mean arterial pressure (MAP), and decreased HR, more than did infusion of ALDO. The changes in MAP in response to both treatments depended on age. For all ages, MAP and saline intake increased simultaneously during ALDO, while MAP always increased before saline intake did during ALDO/DEX20. Contrary to our predictions, MAP did not increase more in old rats in response to either treatment. We speculate that age-related declines in cardiovascular responses to glucocorticoids contributed to the attenuated increases in sodium intake in response to glucocorticoids that were observed in older animals.


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