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1-adrenoceptor stimulation on ventricular
cardiomyocytes from adult rat
Physiologisches Institut, Justus-Liebig-Universität, D-35392 Giessen, Germany
We
investigated whether selective 
1-adrenoceptor
stimulation causes hypertrophic growth on isolated ventricular
cardiomyocytes from adult rat. As parameters for the induction of
hypertrophic growth, the increases of [14C]phenylalanine
incorporation, protein and RNA mass, and cell size were
determined. Isoproterenol (Iso, 10 µM) alone had no growth
effect. In the presence of the 2-adrenoceptor antagonist ICI-118551 (ICI, 10 µM), Iso caused an increase in
[14C]phenylalanine incorporation, protein and RNA mass,
cell volume, and cross-sectional area. We showed for phenylalanine
incorporation that the growth effect of Iso+ICI could be antagonized by
1-adrenoceptor blockade with atenolol (10 µM) or
metoprolol (10 µM), indicating that it was caused by selective
1-adrenoceptor stimulation. The growth response to
Iso+ICI was accompanied by an increase in ornithine decarboxylase (ODC)
activity and expression. Inhibition of ODC by the ODC antagonist
difluoromethylornithine (1 mM) attenuated this hypertrophic response,
indicating that ODC induction is causally involved. The growth response
to Iso+ICI was found to be cAMP independent but was sensitive to
genistein (100 µM) or rapamycin (0.1 µM). The reaction was enhanced
in the presence of pertussis toxin (10 µM). We conclude that
selective 1-adrenoceptor stimulation causes hypertrophic
growth of ventricular cardiomyocytes by a mechanism that is independent
of cAMP but dependent on a tyrosine kinase and ODC.
ornithine decarboxylase; tyrosine kinase; p70s6k
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