The effect of the beta2-adrenoceptor agonist prodrug BRL-47672 on cardiovascular function, skeletal muscle myosin heavy chain, and MyoD expression in the rat

The Journal of Pharmacology and Experimental Therapeutics
S W JonesP L Greenhaff

Abstract

The intracellular mechanisms that regulate changes in postnatal myosin heavy chain (MHC) expression are not well established. The major objective of this study was to examine the acute and chronic effects of administration of BRL-47672, the prodrug of the beta2-adrenoceptor agonist clenbuterol on MHC and MyoD transcription factor expression to determine whether or not changes in MHC composition are preceded by changes in MyoD protein expression. To assess to what extent the use of BRL-47672 minimized cardiovascular effects, its hemodynamic actions were compared with those of clenbuterol. The effect of BRL-47672 on heart rate, mean arterial blood pressure, and hindquarters vascular conductance was significantly less than that of clenbuterol after a single i.p. injection (250 microg kg(-1) body mass). In the main study, 4-week old rats were given BRL-47672 (900 microg kg(-1) body mass) or an equivalent volume of saline (control) daily for 1, 28, or 56 days. Soleus muscle (SOL) was excised and MHC and MyoD expression analyzed. After 4 weeks, SOL from the BRL-47672-treated animals had significantly faster MHC composition (49 +/- 2% MHCIIA) compared with those from the control animal (39 +/- 3% MHCIIA, P <0.05). MyoD expression incr...Continue Reading

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Citations

Jul 28, 2006·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·David J BakerRussell T Hepple
Sep 11, 2009·Current Opinion in Clinical Nutrition and Metabolic Care·René KoopmanGordon S Lynch
Jan 21, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·T G McDaneldD E Moody

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