Relation between contractile function and regulatory cardiac
proteins in hypertrophied hearts.
Stein, Birgitt, Sabine Bartel, Uwe Kirchhefer, Sabine Kokott, Ernst
-Georg Krause, Joachim Neumann, Wilhelm Schmitz, Hasso Scholz.
Abteilung Allgemeine Pharmakologie, Universit[umlaut]ats
-Krankenhaus Eppendorf, Martinistra[beta]e 52, 20246 Hamburg, *Max
-Delbr[umlaut]uck-Centrum f[umlaut]ur Molekulare Medizin, Robert
-R[diaeresis]ossle-Stra[beta]e 10, 13122 Berlin, _Institut f[umlaut]ur
Pharmakologie und Toxikologie, Universit[umlaut]at M[umlaut]unster,
Domagkstra[beta]e 12, 48149 M[umlaut]unster, FRG
APStracts 2:0540H, 1995.
The aim of the study was to examine the mechanism(s) underlying the
reduced isoproterenol-induced positive inotropic and lusitropic
effects in hypertrophied hearts. Chronic [beta]-adrenergic
stimulation (2.4 mg isoproterenol/kg d; 4 days) induced cardiac
hypertrophy by 33+/-2% in rats. Parallel a down-regulation of
phospholamban (PLB) and sarcoplasmic reticulum Ca2+-ATPase (SERCA2)
protein expression by 49% and 40%, respectively, was observed,
whereas troponin I (TNI) and C-protein remained unchanged. In
papillary muscles from chronic [beta]-adrenergic stimulated rats the
isoproterenol-induced positive inotropic and lusitropic effects as
well as cAMP accumulation were attenuated compared to control
animals. Acute exposure to isoproterenol induced a phosphate
incorporation into PLB, TNI and C-protein of 48+/-4.6, 55+/-5.0 and
27+/-4.9 pmol P/mg homogenate protein, respectively, in control
animals. In the hypertrophied hearts only phosphate incorporation
into PLB was reduced by 76%, whereas phosphate incorporation into TNI
or C-protein remained unchanged. In conclusion, chronic [beta]
-adrenergic stimulation reduced the isoproterenol stimulated positive
inotropic and lusitropic effects in papillary muscles which were
accompanied by i) a diminished cAMP formation ii) an attenuation of
cAMP-mediated PLB phosphorylation and iii) a down-regulation of PLB
and SERCA2 protein.
Received 13 March 1995; accepted in final form 20 November 1995.
APS Manuscript Number H235-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95