Chronic β-blockade increases skeletal muscle β-adrenergicreceptor density and enhances contractile force

1997 ◽  
Vol 83 (2) ◽  
pp. 459-465 ◽  
Author(s):  
René J. L. Murphy ◽  
Phillip F. Gardiner ◽  
Guy Rousseau ◽  
Michel Bouvier ◽  
Louise Béliveau
Keyword(s):  
Skeletal Muscle ◽  
Adrenergic Receptor ◽  
Contractile Force ◽  
Medial Gastrocnemius ◽  
Receptor Density ◽  
Sprague Dawley ◽  
Oxidative Potential ◽  
Sprague Dawley Rats ◽  
Adrenergic Antagonist ◽  
Contractile Forces

Murphy, René J. L., Phillip F. Gardiner, Guy Rousseau, Michel Bouvier, and Louise Béliveau. Chronic β-blockade increases skeletal muscle β-adrenergic-receptor density and enhances contractile force. J. Appl. Physiol.83(2): 459–465, 1997.—The effects of a chronic 14-day administration of a selective β2-adrenergic-receptor antagonist (ICI-118551) on skeletal muscle were evaluated in female Sprague-Dawley rats. Chronic ICI-118551 treatment did not modify muscle mass, oxidative potential, or protein concentration of the medial gastrocnemius muscle, suggesting that maintenance of these skeletal muscle characteristics is not dependent on β2-adrenergic-receptor stimulation. However, the drug treatment increased β-adrenergic-receptor density of the lateral gastrocnemius (42%) and caused an increase in specific (g/g) isometric in situ contractile forces of the medial gastrocnemius [twitch, 56%; tetanic (200 Hz), 28%]. The elevated contractile forces observed after a chronic treatment with ICI-118551 were completely abolished when the β2-adrenergic antagonist was also administered acutely before measurement of contractile forces, suggesting that this response is β2-adrenergic-receptor dependent. Possible mechanisms for the increased forces were studied. Caffeine administration potentiated twitch forces but had little effect on tetanic force in control animals. Administration of dibutyryl adenosine 3′,5′-cyclic monophosphate in control animals also resulted in small increases of twitch force but did not modify tetanic forces. We conclude that increases in β-adrenergic-receptor density and the stimulation of the receptors by endogenous catecholamines appear to be responsible for increased contractile forces but that the mechanism remains to be demonstrated.

A farnesyltransferase inhibitor attenuated β-adrenergic receptor downregulation in rat skeletal muscle

2002 ◽  
Vol 282 (1) ◽  
pp. R317-R322 ◽  
Author(s):  
Julie L. Lavoie ◽  
Angelino Calderone ◽  
Louise Béliveau
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Adrenergic Receptor ◽  
Cardiac Fibroblasts ◽  
Medial Gastrocnemius ◽  
Sprague Dawley ◽  
Farnesyltransferase Inhibitor ◽  
Concurrent Administration ◽  
Sprague Dawley Rats ◽  
Muscle Types

Farnesylation represents an essential posttranslational modification of several well-defined proteins implicated in the homologous desensitization of the β-adrenergic receptor (β-ADR). The following study examined the effect of a novel farnesyltransferase inhibitor, BMS-191563, on agonist-mediated β-ADR downregulation in skeletal muscle. Female Sprague-Dawley rats were treated for 12 days with the β2-adrenergic agonist clenbuterol (4 mg/kg) with or without the concurrent administration of BMS-191563 (2 mg · kg−1 · day−1). Clenbuterol promoted gastrocnemius muscle hypertrophy, whereas the soleus muscle was unaffected. Total β-ADR density was decreased by 45 and 40% in the soleus and medial gastrocnemius (MG), respectively, after clenbuterol treatment. BMS-191563 treatment did not prevent clenbuterol-stimulated MG hypertrophy, but markedly attenuated β-ADR downregulation in both muscle types. This latter effect in the soleus muscle was not associated with the inhibition of Ras farnesylation. Likewise, in rat cardiac fibroblasts, isoproterenol-mediated decrease of total β-ADR density was abrogated by the prior treatment with BMS-191563. Collectively, these data demonstrate that the mechanism(s) implicated in agonist-mediated β-ADR downregulation was sensitive to BMS-191563, thereby suggesting the involvement of farnesylated proteins.

scholarly journals Trafficking of dietary oleic, linolenic, and stearic acids in fasted or fed lean rats

2000 ◽  
Vol 278 (6) ◽  
pp. E1124-E1132 ◽  
Author(s):  
Daniel H. Bessesen ◽  
S. Holly Vensor ◽  
Matthew R. Jackman
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Stearic Acid ◽  
Dietary Fat ◽  
Medial Gastrocnemius ◽  
Sprague Dawley ◽  
Fed State ◽  
Liquid Meal ◽  
Fasted State ◽  
Sprague Dawley Rats

Increasing evidence supports the notion that there are significant differences in the health effects of diets enriched in saturated, as opposed to monounsaturated or polyunsaturated fat. However, the current understanding of how these types of fat differ in their handling by relevant tissues is incomplete. To examine the effects of fat type and nutritional status on the metabolic fate of dietary fat, we administered 14C-labeled oleic, linolenic, or stearic acid with a small liquid meal to male Sprague-Dawley rats previously fasted for 15 h (fasted) or previously fed ad libitum (fed).14CO2 production was measured for 8 h after tracer administration. The 14C content of gastrointestinal tract, serum, liver, skeletal muscle (soleus, lateral, and medial gastrocnemius), and adipose tissue (omental, retroperitoneal, and epididymal) was measured at six time points (2, 4, 8, 24, and 48 h and 10 days) after tracer administration. Plasma levels of glucose, insulin, and triglyceride were also measured. Oxidation of stearic acid was significantly less than that of either linolenic or oleic acid in both the fed and fasted states. This reduction was in part explained by a greater retention of stearic acid within skeletal muscle and liver. Oxidation of oleate and stearate were significantly lower in the fed state than in the fasted state. In the fasted state, liver and skeletal muscle were quantitatively more important than adipose tissue in the uptake of dietary fat tracers during the immediate postprandial period. In contrast, adipose tissue was quantitatively more important than skeletal muscle or liver in the fed state. The movement of carbons derived from dietary fat between tissues is a complex time-dependent process, which varies in response to the type of fat ingested and the metabolic state of the organism.

Effect of low-potassium diet on rat exercise hyperthermia and heatstroke mortality

1981 ◽  
Vol 51 (1) ◽  
pp. 8-13 ◽  
Author(s):  
R. W. Hubbard ◽  
M. Mager ◽  
W. D. Bowers ◽  
I. Leav ◽  
G. Angoff ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Plasma Potassium ◽  
Heat Illness ◽  
Sprague Dawley ◽  
Heat Gain ◽  
Sprague Dawley Rats ◽  
Low Potassium ◽  
Work Done ◽  
Low K

A total of 182 male Sprague-Dawley rats weighing 250–300 g were fed either a control (n = 122) diet for 32 days. The diets contained either 125 or 8 meq potassium/kg, respectively. Rats fed the low-K diet gained weight at only one-third the rate of controls (1.7 vs. 5.2 g/day), and their skeletal muscle and plasma potassium levels were reduced by 28 and 47%, respectively. When run to exhaustion at either 15 or 20 degrees C, low K+-fed rats accomplished less than one-half of the work done by the controls (26 vs. 53 kg. m) but exhibited a markedly greater rate of heat gain per kilogram-meter of work than controls (0.12 vs. 0.05 degrees C)ambient temperature of 20 degrees C, the rats of the low-K+ group despite large differences in body weight (-25%), run time temperature and twice (33 vs 17%) the mortality rate of the controls. Postexercise increases in circulating potassium (less than 90%) of heat-injured rats raised the plasma levels of low K+-fed rats to normal (5.9 +/- 2.2 meq/l). These results appear to characterize the existence of an insidious and, therefore, undocumented form of fatal exertion-induced heat illness.

Chronic intermittent hypoxia alters NE reactivity and mechanics of skeletal muscle resistance arteries

2006 ◽  
Vol 100 (4) ◽  
pp. 1117-1123 ◽  
Author(s):  
Shane A. Phillips ◽  
E. B. Olson ◽  
Julian H. Lombard ◽  
Barbara J. Morgan
Keyword(s):  
Skeletal Muscle ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Physiological Salt Solution ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Sprague Dawley Rats ◽  
Resting Tone ◽  
Wall Distensibility

Although arterial dilator reactivity is severely impaired during exposure of animals to chronic intermittent hypoxia (CIH), few studies have characterized vasoconstrictor responsiveness in resistance arteries of this model of sleep-disordered breathing. Sprague-Dawley rats were exposed to CIH (10% inspired O2 fraction for 1 min at 4-min intervals; 12 h/day) for 14 days. Control rats were housed under normoxic conditions. Diameters of isolated gracilis muscle resistance arteries (GA; 120–150 μm) were measured by television microscopy before and during exposure to norepinephrine (NE) and angiotensin II (ANG II) and at various intraluminal pressures between 20 and 140 mmHg in normal and Ca2+-free physiological salt solution. There was no difference in the ability of GA to constrict in response to ANG II ( P = 0.42; not significant; 10−10–10−7 M). However, resting tone, myogenic activation, and vasoconstrictor responses to NE ( P < 0.001; 10−9–10−6 M) were reduced in CIH vs. controls. Treatment of rats with the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol; 1 mM) in the drinking water restored myogenic responses and NE-induced constrictions of CIH rats, suggesting that elevated superoxide production during exposure to CIH attenuates vasoconstrictor responsiveness to NE and myogenic activation in skeletal muscle resistance arteries. CIH also leads to an increased stiffness and reduced vessel wall distensibility that were not correctable with oral tempol treatment.

Mammalian target of rapamycin pathway is up-regulated by both acute endurance exercise and chronic muscle contraction in rat skeletal muscle

2013 ◽  
Vol 38 (8) ◽  
pp. 862-869 ◽  
Author(s):  
Brittany A. Edgett ◽  
Melanie L. Fortner ◽  
Arend Bonen ◽  
Brendon J. Gurd
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Gastrocnemius Muscle ◽  
Contractile Activity ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

This study examined changes in the expression of translation initiation regulatory proteins and mRNA following both an acute bout of endurance exercise and chronic muscle contractile activity. Female Sprague Dawley rats ran for 2 h at 15 m·min−1 followed by an increase in speed of 5 m·min−1 every 5 min until volitional fatigue. The red gastrocnemius muscle was harvested from nonexercised animals (control; n = 6) and from animals that exercised either immediately after exercise (n = 6) or following 3 h of recovery from exercise (n = 6). Compared with control, ribosomal protein S6 (rpS6) mRNA was elevated (p < 0.05) at both 0 h (+32%) and 3 h (+47%). Both a catalytic subunit of eukaryotic initiation factor 2B (eIF2Bε) (+127%) and mammalian target of rapamycin (mTOR) mRNA (+44%) were increased at 3 h, compared with control. Phosphorylation of mTOR (+40%) and S6 kinase 1 (S6K1) (+266%) were increased immediately after exercise (p < 0.05). Female Sprague Dawley rats also underwent chronic stimulation of the peroneal nerve continuously for 7 days. The red gastrocnemius muscle was removed 24 h after cessation of the stimulation. Chronic muscle stimulation increased (p < 0.05) mTOR protein (+74%), rpS6 (+31%), and eukaryotic initiation factor 2α (+44%, p = 0.069), and this was accompanied by an increase in cytochrome c (+31%). Increased resting phosphorylation was observed for rpS6 (+51%) (p < 0.05) but not for mTOR or eukaryotic initiation factor 4E binding protein 1. These experiments demonstrate that both acute and chronic contractile activity up-regulate the mTOR pathway and mitochondrial content in murine skeletal muscle. This up-regulation of the mTOR pathway may increase translation efficiency and may also represent an important control point in exercise-mediated mitochondrial biogenesis.

In vivo leucine oxidation at rest and during two intensities of exercise

1982 ◽  
Vol 53 (4) ◽  
pp. 947-954 ◽  
Author(s):  
P. W. Lemon ◽  
F. J. Nagle ◽  
J. P. Mullin ◽  
N. J. Benevenga
Keyword(s):  
Skeletal Muscle ◽  
Specific Activity ◽  
Muscle Metabolism ◽  
Weighted Average ◽  
Mixed Diet ◽  
Sprague Dawley ◽  
Tracer Dose ◽  
Sprague Dawley Rats ◽  
14Co2 Production

After ingestion of a mixed diet containing a tracer dose (10 muCi) of L-[1–14C]leucine (Leu), 32 male Sprague-Dawley rats (70–90 g) remained at rest (R) or completed 1 h exercise at 80 (E80) or 40% VO2max (E40). 14CO2 production was assessed for 6 h (exercise occurred from h 2 to 3). Four rats were killed at 2, 3, 4, and 6 h (R), at 3 and 6 h (E80), and at 6 h (E40). Determinations were 1) tissue specific activity dpm X mumol-1 from a) mixed skeletal muscle (gastrocnemius, soleus, quadriceps, and hamstrings) and b) liver and 2) radioactivity remaining in the gastrointestinal tract (GIT). Leu oxidized (mumol) was estimated (14 CO2 dpm X tissue sp act dpm-1 X mumol-1) independently from skeletal muscle and liver. Results were 1) 14CO2 production increased in both E80 and E40 compared with R (P less than 0.05), 2) E80 14CO2 increase was greater than E40 (P less than 0.05), 3) GIT absorption was reduced in E80 and E40 compared with R (P less than 0.05), and 4) exercise Leu oxidation (weighted average of tissue estimates) was 26% greater than R (P less than 0.05). The origin and site of the increased Leu oxidation cannot be determined from the present data; however, due to the magnitude of increase in skeletal muscle metabolism relative to other tissues during exercise, it is probable that skeletal muscle plays a significant role.

Both peripheral chylomicron catabolism and hepatic uptake of remnants are defective in nephrosis

1992 ◽  
Vol 263 (2) ◽  
pp. F335-F341
Author(s):  
G. A. Kaysen ◽  
L. Mehendru ◽  
X. M. Pan ◽  
I. Staprans
Keyword(s):  
Skeletal Muscle ◽  
Nephrotic Syndrome ◽  
Potential Risk ◽  
Vascular Endothelium ◽  
Hepatic Uptake ◽  
Absolute Rate ◽  
Sprague Dawley ◽  
Primary Defect ◽  
Heymann Nephritis ◽  
Sprague Dawley Rats

We showed previously that proteinuria caused delayed chylomicron (CM) clearance in the rat and postulated the existence of a primary defect in CM hydrolysis. It was possible that reduced CM clearance resulted from increased lipogenesis causing saturation of catabolic sites and not from a primary defect in CM catabolism. To clarify this point we measured kinetically the absolute rate of triglyceride (TG) uptake from CM in rats with Heymann nephritis (HN) and normal Sprague-Dawley rats (SD) and determined TG uptake in individual tissues using [3H]TG- and [14C]cholesterol-labeled CM. Hepatic [14C]cholesterol uptake was reduced in HN (69.3 +/- 6 vs. 7.2 +/- 2% of dose, P less than 0.001). TG uptake was reduced in HN measured kinetically (1.01 +/- 0.09 vs. 0.213 +/- 0.028 mg TG.min-1.100 g body wt-1, P less than 0.001) and reduced in all tissues (heart, skeletal muscle, fat, and liver). CM are catabolized on the vascular endothelium to atherogenic, cholesterol-rich remnant (CM remnant) particles, which are then rapidly taken up by the liver. We measured hepatic CM remnant uptake in SD and in HN using [14C]cholesterol-labeled CM remnant. CM remnant uptake was significantly reduced in HN (58 +/- 1.2 vs. 20 +/- 0.86% uptake, P less than 0.01). CM remnants were increased significantly in plasma of HN. Thus the nephrotic syndrome causes a primary defect in the uptake of TG from CM that is expressed in all tissues and a separate defect in hepatic CM remnant uptake. Although CM remnant generation is impaired because of defective CM hydrolysis, the defect in hepatic CM remnant uptake is so severe that these particles accumulate in blood, posing a potential risk for atherogenesis.

Skeletal muscle beta-adrenoceptor distribution and responses to isoproterenol in hyperthyroidism

1992 ◽  
Vol 262 (4) ◽  
pp. E504-E510 ◽  
Author(s):  
W. H. Martin ◽  
E. Korte ◽  
T. K. Tolley ◽  
J. E. Saffitz
Keyword(s):  
Skeletal Muscle ◽  
Adrenergic Receptor ◽  
Human Skeletal Muscle ◽  
Muscle Fibers ◽  
Type I ◽  
Receptor Density ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Isoproterenol Infusion

To determine whether hyperthyroidism selectively increases beta-adrenergic receptor density in vessels or fibers of human skeletal muscle, we characterized beta-receptor distribution autoradiographically in muscle biopsies of 18 subjects aged 26 +/- 1 yr before and after daily administration of 100 micrograms 3,5,3'-triiodothyronine (T3) for 2 wk. To establish whether vascular and metabolic responses to beta-adrenergic stimulation are concomitantly altered, we quantified calf blood flow and plasma concentrations of glucose, lactate, glycerol, free fatty acids (FFA), insulin, and C-peptide during graded-dose isoproterenol infusion in eight of these individuals. Differences in beta-adrenergic receptor density among muscle fiber types and vascular components were highly significant (type I greater than type IIa greater than type IIb muscle fibers, P less than 0.001; and type I muscle fibers greater than resistance arterioles, P less than 0.05). Hyperthyroidism increased beta-adrenergic receptor density in all types of muscle fibers (+31-50%; P less than 0.01) but not in resistance arterioles. There was no change in calf blood flow or plasma glucose, glycerol, FFA, insulin, or C-peptide responses to isoproterenol. A rise in lactate during stages 3 and 4 of isoproterenol infusion (P less than 0.01) was observed before but not after T3 administration. Thus hyperthyroidism increases beta-adrenergic receptor density in fibers but not vessels of human skeletal muscle without increasing either metabolic or vascular responses to selective beta-adrenergic stimulation.

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