Selective activation of alpha1A-adrenergic receptors in neonatal cardiac myocytes is sufficient to cause hypertrophy and differential regulation of alpha1-adrenergic receptor subtype mRNAs

J Mol Cell Cardiol. 1998 Aug;30(8):1515-23. doi: 10.1006/jmcc.1998.0717.


Prolonged stimulation of cardiac alpha1-adrenergic receptors causes myocyte hypertrophy, although the receptor subtypes involved remain controversial. We have used a potent and selective alpha1A agonist, A-61603, to test whether activation of the alpha1A-adrenergic receptor subtype is sufficient to mediate the morphological, biochemical and molecular alterations associated with cardiomyocyte hypertrophy. In neonatal rat cardiomyocyte cultures, 48 h incubation with 50 nm A-61603 led to a marked increase in myocardial cell size that was associated with a significant elevation in the rate of protein synthesis. The increased rate of incorporation of radiolabelled amino acids into protein stimulated by A-61603 was totally abolished by the selective alpha1A antagonist KMD-3213. A-61603 increased ANF secretion three-fold, and ANF mRNA 12-fold above control levels in cardiomyocyte cultures. RNase protection analysis demonstrated a A-61603-mediated two to three-fold increase in alpha1A-adrenergic receptor mRNA with a concomitant 50% decrease in alpha1B mRNA levels by 48 h. Identical responses of differential regulation of alpha1A- and alpha1B-adrenergic receptor mRNA were observed with phenylephrine. Both the stimulation of alpha1A- and repression alpha1B-adrenergic receptor mRNA caused by A-61603 could be abolished by 10-20 nm KMD-3213. The present data provide evidence that selective activation of alpha 1A-adrenergic receptors on cardiomyocytes is sufficient to mediate the phenotypic changes associated with cardiac hypertrophy. In addition, the differential regulation of alpha1A and alpha1B mRNA in response to selective alpha1A-adrenergic receptor stimulation suggests that cross-talk between receptor subtypes may be involved in regulating receptor populations during chronic agonist exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Animals, Newborn
  • Atrial Natriuretic Factor / metabolism
  • Cardiomegaly / pathology*
  • Cells, Cultured
  • Heart / growth & development
  • Imidazoles / pharmacology
  • Indoles / pharmacology
  • Myocardium / cytology*
  • Propranolol / pharmacology
  • Proteins / metabolism
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / genetics*
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Tetrahydronaphthalenes / pharmacology


  • A 61603
  • Adra1a protein, rat
  • Adra1b protein, rat
  • Adrenergic alpha-Agonists
  • Imidazoles
  • Indoles
  • Proteins
  • RNA, Messenger
  • Receptors, Adrenergic, alpha-1
  • Tetrahydronaphthalenes
  • Atrial Natriuretic Factor
  • Propranolol
  • silodosin