Beta-adrenergic cardiac hypertrophy is mediated primarily by the beta(1)-subtype in the rat heart

J Mol Cell Cardiol. 2001 Mar;33(3):561-73. doi: 10.1006/jmcc.2000.1332.


Myocardial beta-adrenergic receptors (beta -ARs) consist of beta(1)- and beta(2)-subtypes, which mediate distinct signaling mechanisms. We examined which beta-AR subtype mediates cardiac hypertrophy. The beta(2)-subtype is predominant in neonatal rat cardiac myocytes (beta(1), 36%vbeta(2), 64%), while the beta(1)-subtype predominates in the adult rat heart (59%v 41%). Stimulation of cultured cardiac myocytes in vitro with isoproterenol (ISO), an agonist for beta(1)- and beta(2)-ARs, caused hypertrophy of myocytes along with increases in transcription of atrial natriuretic factor (ANF) and actin reorganization. All of these ISO-mediated myocyte responses in vitro were inhibited by a beta(1)-AR antagonist, betaxolol, but not by a beta(2)-AR antagonist, ICI 118551. Pertussis toxin failed to affect ISO-induced increases in total protein/DNA content and ANF transcription in vitro. ISO increased LV weight/body weight and ANF transcription in the adult rat in vivo, which were also inhibited by betaxolol but not by ICI 118551. These results suggest that beta -AR stimulated hypertrophy is mediated by the beta(1)-subtype and by a pertussis toxin-insensitive mechanism

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Animals, Newborn
  • Atrial Natriuretic Factor / metabolism
  • Cardiomegaly / metabolism*
  • Cell Size
  • Cells, Cultured
  • Heart
  • Heart Ventricles / cytology
  • Heart Ventricles / metabolism*
  • Isoproterenol / pharmacology
  • Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta-1 / biosynthesis
  • Receptors, Adrenergic, beta-1 / metabolism*
  • Receptors, Adrenergic, beta-2 / biosynthesis
  • Receptors, Adrenergic, beta-2 / metabolism


  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-Agonists
  • Proteins
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Atrial Natriuretic Factor
  • Isoproterenol