Clenbuterol favorably remodels neonatal cardiac cells via activation of p38 MAPK signalling pathway

J Cardiovasc Surg (Torino). 2012 Dec;53(6):789-95.


Aim: Pharmacologic treatments which aim to induce physiological hypertrophy are now thought as novel treatments for heart failure. Thus, clenbuterol, a beta-2 adrenergic agonist has recently been shown to partially reverse cardiac remodeling by inducing physiological hypertrophy. The present study further investigated potential underlying mechanisms of this effect in a neonatal cardiomyocytes cell based model.

Methods: Neonatal cardiomyocytes obtained from newborn rats were exposed to clenbuterol (CLEN, 1μM) for five days, while untreated cells served as controls. CLEN administration resulted in well organized orientation of cytoskeletal fibers manifesting as a longitudinal cell shape, while had no effect on myosin heavy chain (MHC) isoform expression. CLEN increased cell growth as indicated by protein content: total protein per cell (pg/cell) was 116 (6.0) for CLEN and 77 (5.0) for the untreated cells, P<0.05. This response was accompanied by a 2.2 fold increase in phospho-p38 MAPK levels as compared to untreated cells, P<0.05 while no changes were observed in ERK, JNK and Akt. Administration of SB203580 (a p38 MAPK inhibitor) abrogated the CLEN induced changes in cardiomyocyte morphology, while it had no effect on protein content.

Conclusion: Clenbuterol induces favorable changes in neonatal cardiomyocyte shape and geometry without affecting MHC isoform expression. Activation of p38 MAPK signaling seems, at least in part, to be implicated in this response.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Animals, Newborn
  • Cell Culture Techniques
  • Cell Shape / drug effects*
  • Clenbuterol / pharmacology*
  • Cytoskeleton / drug effects
  • MAP Kinase Signaling System / drug effects*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / pathology
  • Myocytes, Cardiac / physiology
  • Myosin Heavy Chains / metabolism
  • Protein Isoforms / metabolism
  • Rats
  • p38 Mitogen-Activated Protein Kinases / drug effects*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Adrenergic beta-Agonists
  • Protein Isoforms
  • p38 Mitogen-Activated Protein Kinases
  • Myosin Heavy Chains
  • Clenbuterol