Isoproterenol infusion induces alterations in expression of
hypertrophy-associated genes in rat heart.
Boluyt, Marvin O., Xilin Long, Thomas Eschenhagen, Ulrike Mende,
Wilhelm Schmitz, Michael T. Crow, and Edward G. Lakatta.
Laboratory of Cardiovascular Science, Gerontology Research Center,
National Institute on Aging, Baltimore, MD 21224 USA, and Abteilung
Allgemeine Pharmakologie, Universitats-Krankenhaus Eppendorf, D-20246
Hamburg, FRG
APStracts 2:0094H, 1995.
Chronic infusion of isoproterenol (ISO) in rats results in cardiac
hypertrophy via incompletely understood mechanisms. Our purpose was
to determine whether ISO infusion would alter the expression of genes
associated with hypertrophy. Male Wistar rats received either 2.4
mg/kg ISO/day, 9.9 mg/kg/day propranolol (PROP), both ISO and PROP,
or vehicle (NaCl) via subcutaneously implanted osmotic pumps. In ISO
rats, the ventricular weight/body weight ratio was increased by 27%
after 1 day and peaked on day 3 (+40%). The levels of atrial
natriuretic factor (ANF) and fibronectin (FN) mRNA in the left
ventricles were elevated 20-fold and 13-fold in ISO rats,
respectively, peaking at 3-days of infusion. The increase in FN mRNA
accumulation was at least partially accounted for by elevated
expression of the EIIIA and EIIIB splicing variants. Levels of
transforming growth factor [beta]1 (TGF[beta]1) mRNA were elevated 2
-fold after 3 days of ISO infusion. The abundance of skeletal [alpha]
-actin (SK) mRNA increased 4-fold after 1 day of ISO, and declined
thereafter. ISO infusion decreased sarcoplasmic reticulum Ca2+ ATPase
(SERCA) and preproenkephalin (PNK) gene expression by nearly equal to
50% and induced a myosin heavy chain (MHC) isogene switch favoring
[beta]-MHC. PROP partially inhibited the ISO-evoked increases in ANF
and FN mRNA, completely prevented the ISO-induced changes in
TGF[beta]1 and SERCA mRNA, but had no effect on the ISO-stimulated
changes in SK and PNK gene expression. These results demonstrate that
chronic ISO infusion elicits alterations in cardiac gene expression
that are consistent with the development of myocyte hypertrophy and
interstitial fibrosis, and are directionally identical to those
previously reported for pressure-overload hypertrophy.
Received 4 May 1994; accepted in final form 27 February 1995.
APS Manuscript Number H391-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.