The effect of the anabolic agent, clenbuterol, on overloaded rat skeletal muscle

Maltin, C A; Delday, Margaret Inkster; Hay, Susan M.; Smith, F. G. Walton; Lobley, G. E.; Reeds, Peter J.

doi:10.1007/bf01121878

Cited by 39 publications

(32 citation statements)

References 9 publications

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“…The ratio of heart weight to tibial length significantly increased in Clen-treated animals. However, the ratio of heart weight to body weight did not change after Clen administration, presumably because of the increase in body weight due to skeletal muscle hypertrophy (3,7,16). It could be argued that after the increase in body mass, a proportional increase in cardiac output and blood flow is expected; the myocyte hypertrophy observed could therefore be the consequence of pressure-volume overload rather than a direct effect of Clen.…”

Section: Discussionmentioning

confidence: 94%

Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle

Soppa¹,

Smolenski²,

Latif³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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. Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle. Am J Physiol Heart Circ Physiol 288: H1468 -H1476, 2005. First published November 4, 2004 doi: 10.1152/ajpheart.00624.2004, a ␤2-agonist, is known to produce skeletal and myocardial hypertrophy. This compound has recently been used in combination with left ventricular assist devices for the treatment of end-stage heart failure to reverse or prevent the adverse effects of unloading-induced myocardial atrophy. However, the mechanisms of action of Clen on myocardial cells have not been fully elucidated. In an attempt to clarify this issue, we examined the effects of chronic administration of Clen on Ca 2ϩ handling and substrate preference in cardiac muscle. Rats were treated with either 2 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 Clen or saline (Sal) for 4 wk with the use of osmotic minipumps. Ventricular myocytes were enzymatically dissociated. Cells were field stimulated at 0.5, 1, and 2 Hz, and cytoplasmic Ca 2ϩ transients were monitored with the use of the fluorescent indicator indo-1 acetoxymethyl ester. Two-dimensional surface area and action potentials in current clamp were also measured. We found that in the Clen group there was significant hypertrophy at the organ and cellular levels compared with Sal. In Clen myocytes, the amplitude of the indo-1 ratio transients was significantly increased. Sarcoplasmic reticulum Ca 2ϩ content, estimated by rapid application of 20 mM caffeine, was significantly increased in the Clen group. The action potential was prolonged in the Clen group compared with Sal. Carbohydrate contribution to the tricarboxylic cycle (Krebs cycle) flux was increased several times in the Clen group. This increase was associated with decreased expression of peroxisome proliferator-activated receptor-␣. This study shows that chronic administration of Clen induces cellular hypertrophy and increases oxidative carbohydrate utilization together with an increase in sarcoplasmic reticulum Ca 2ϩ content, which results in increased amplitude of the Ca 2ϩ transients. These effects could be important when Clen is used in conjunction with left ventricular assist devices treatment.sarcoplasmic reticulum Ca 2ϩ content; tricarboxylic cycle; left ventricular assist devices LONG-TERM LEFT VENTRICULAR (LV) assist device (LVAD) support has been shown to improve survival and quality of life in patients with advanced heart failure and contraindications to cardiac transplantation (22). LVAD support is also routinely used as a bridge to transplantation in patients with end-stage heart failure. In a number of patients, with the use of this strategy in association with pharmacological therapy (combination therapy), a significant improvement in myocardial performance has been observed. In some cases the mechanical device could be explanted without resorting to heart transplantation ("bridge to recovery") (11-13, 27, 40).LVAD support results in profound and complex changes in the structure and function of the myocardium, which include "...

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Section: Discussionmentioning

confidence: 94%

Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle

Soppa¹,

Smolenski²,

Latif³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…Increased muscle mass and contractility after administration of 2 agonists have been explained by increased protein synthesis, decreased protein degradation, changes in water content, changes in phosphorylation of intracellular proteins and, possible androgenic activity (Reeds et al 1986;Maltin et al 1987;Zeman et al 1987;Claeys et al 1989;Bates and Pell 1991;Benson et al1991;Cartaña and Stock 1994;Cartaña and Stock 1995;Dodd et al 1996;Von Bueren et al 2007). An involvement of L-type calcium channels has been found to be an unlikely contributor (Murphy et al 1999a).…”

Section: Discussionmentioning

confidence: 96%

Effects of β2-adrenergic stimulation on exercise capacity in normal subjects

et al. 2011

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β2-Adrenergic receptor agonists are believed to present with ergogenic properties. However, how combined respiratory, cardiovascular and muscular effects of these drugs might affect exercise capacity remain incompletely understood. The effects of salbutamol were investigated in 23 healthy subjects. The study was randomised, placebo-controlled in double-blind and followed a cross-over design. Salbutamol was given at the dose of 10 μg/min in 11 subjects and 20 μg/min iv in the other 12 subjects. Measurements included muscle sympathetic nerve activity (MSNA), ventilatory responses to hyperoxic hypercapnia (7% CO(2) in O(2,) central chemoreflex), isocapnic hypoxia (10% O(2) in N(2), peripheral chemoreflex) and isometric muscle contraction followed by a local circulatory arrest (metaboreflex), cardiopulmonary exercise test (CPET) variables and isokinetic muscle strength. Salbutamol 10 μg/min increased heart rate and blood pressure, while MSNA burst frequency remained unchanged. Peripheral chemosensitivity increased, as evidenced by an increased ventilatory response to hypoxia, but ventilatory responses to hypercapnia or muscle ischaemia remained unchanged. The effects of salbutamol 20 μg/min were similar. Both doses of salbutamol did not affect CPET. Only the higher dose of salbutamol decreased the anaerobic threshold, but this was not associated with a change in VO(2) max. Salbutamol increased the slopes of ventilation as a function of VO(2) (P < 0.05) and VCO(2) (P < 0.001) during CPET. Maximal isokinetic muscle strength was not affected by salbutamol. In conclusion, the acute administration of either low or high dose salbutamol does not affect exercise capacity in normal subjects, in spite of an earlier anaerobic threshold and increased chemosensitivity.

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“…Total RNA was reverse transcribed using an oligo(dT) 18 as previously described [32]. Reverse transcription was carried out at +42°C for 1 h and reverse transcriptase was inactivated by heating at +95°C for 5 min.…”

Section: Gene Expression Analysismentioning

confidence: 99%

“…Clenbuterol, a β2-adrenergic-receptor agonist, specifically promotes growth of cardiac and skeletal muscles in mammals [18,30,33]. This drug is mainly used as a bronchodilator [25] in asthmatic-patient treatments [1,14], but its anabolic properties lead to its illegal use in animal meat production [20] and also in athlete-doping [26,34] in explosive specialities like sprint, weight-lifting or bodybuilding [10,28].…”

Section: Introductionmentioning

confidence: 99%

Molecular impact of clenbuterol and isometric strength training on rat EDL muscles

Mounier¹,

Cavalié²,

Lac³

et al. 2006

Pflugers Arch - Eur J Physiol

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Clenbuterol, a beta2-adrenergic-receptor agonist, is known to provoke muscle hypertrophy and a slow-to-fast phenotype change. A more glycolytic phenotype should be paralleled by changes in muscle glycolytic metabolism. Two groups (n=16 for each) of 3-month-old male Wistar rats (UCL: untrained clenbuterol, and ECL: exercised clenbuterol) received a chronic administration of clenbuterol (2 mg/kg body weight/day). Two other groups of animals (U: untrained and E: exercised), were given a 0.9% NaCl solution instead of clenbuterol. E and ECL animals followed an 8-week progressive isometric force strength-training program. Both clenbuterol administration and training resulted in an increase in extensor digitorum longus (EDL) mass despite the fact that this muscle was indirectly mobilised during isometric force strength training. Clenbuterol and training induced a consistent slow-to-fast phenotype change without drastically increasing specific activities of glycolytic enzymes. Except for GAPDH and hexokinase, modifications in glycolytic-enzyme-specific activities were not explained by transcriptional changes. Lactate dehydrogenase activity was not affected by clenbuterol but was strongly augmented by training. In EDL of ECL rats, both treatments presented an opposite effect compensating each other. GLUT1 mRNA expression was augmented in EDL of UCL and ECL animals, whereas monocarboxylate transporter 1 mRNA amounts were decreased in EDL of UCL rats. Citrate synthase activity was reduced by clenbuterol treatment but remained unchanged in EDL of E animals. Creatine kinase activity was enhanced only by clenbuterol alone. These data show that clenbuterol-induced muscle hypertrophy and slow-to-fast phenotype changes are not associated with a glycolytic-enzyme-activity increase. They also suggest that in EDL isometric force strength training can reverse clenbuterol-induced molecular adaptations.

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The effect of the anabolic agent, clenbuterol, on overloaded rat skeletal muscle

Cited by 39 publications

References 9 publications

Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle

Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle

Effects of β2-adrenergic stimulation on exercise capacity in normal subjects

Molecular impact of clenbuterol and isometric strength training on rat EDL muscles

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