title: Beta-adrenoceptor stimulation attenuates the hypertrophic effect of alpha-adrenoceptor stimulation in adult rat ventricular cardiomyocytes.
abstract: OBJECTIVE
  The study investigated whether beta-adrenoceptor antagonists augment the hypertrophic response of cardiomyocytes evoked by norepinephrine.
  
  
  BACKGROUND
  In adult ventricular cardiomyocytes, stimulation of alpha- but not beta-adrenoceptors induces myocardial hypertrophy. Natural catecholamines, like norepinephrine, stimulate simultaneously alpha- and beta-adrenoceptors. We investigated whether beta-adrenoceptor stimulation interferes with the hypertrophic response caused by alpha-adrenoceptor stimulation.
  
  
  METHODS
  Adult ventricular cardiomyocytes isolated from rats were used as an experimental model. Hypertrophic parameters under investigation were stimulation of phenylalanine incorporation and protein mass, stimulation of 14C-uridine incorporation and RNA mass, and increases in cell shape.
  
  
  RESULTS
  Norepinephrine (0.01 to 10 micromol/liter) increased concentration-dependent phenylalanine incorporation; pEC50 value was 5.9 +/- 0.1 (n = 8). The alpha1-adrenoceptor antagonist prazosin (0.1 micromol/liter) suppressed norepinephrine-induced increase in rate of protein synthesis. Conversely, propranolol (1 micromol/liter) and the beta1-adrenoceptor selective antagonists CPG 20712A (300 nmol/liter) or atenolol (1 micromol/liter) augmented increases in phenylalanine incorporation caused by norepinephrine. Addition of the beta2-adrenoceptor antagonist ICI 118,551 (55 nmol/liter) did not influence the hypertrophic effect of norepinephrine. Atenolol augmented the norepinephrine-induced increases of all hypertrophic parameters investigated (i.e., protein mass, uridine incorporation, RNA mass, cell volume, and cross-sectional area). In the presence of norepinephrine, inhibition of beta1-adrenoceptors increased the amount of protein kinase C-alpha and -delta isoforms translocated into the particulate fraction. The effect of pharmacological inhibition of beta1-adrenoceptors could be mimicked by Rp-cAMPS (adenosine-3', 5'-cyclic phosphorothiolate-Rp). The inhibitory effect of beta1-adrenoceptor stimulation on the alpha-adrenoceptor-mediated effect persisted in cardiomyocytes isolated from hypertrophic hearts of rats submitted to aortic banding.
  
  
  CONCLUSIONS
  In isolated ventricular cardiomyocytes from rats, beta1-adrenoceptor stimulation attenuates the hypertrophic response evoked by alpha1-adrenoceptor stimulation.
authors.affiliation: Physiologisches Institut, Justus-Liebig-Univeristät Giessen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schäfer
authors.forename: K
authors.initials: K
authors.lastname: Pönicke
authors.forename: I
authors.initials: I
authors.lastname: Heinroth-Hoffmann
authors.forename: O E
authors.initials: OE
authors.lastname: Brodde
authors.forename: H M
authors.initials: HM
authors.lastname: Piper
authors.forename: K D
authors.initials: KD
authors.lastname: Schlüter
mesh_terms: D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000473:pathology*; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
chemical_list: D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine