The purpose of this study was to test the relationship between biochemical and functional changes accompanying beta-agonist induced
cardiac hypertrophy and the activation of a
calcium stimulated
cysteine protease. Because the ultrastructural and ionic changes accompanying beta-agonist induced
cardiac hypertrophy are reminiscent of the actions of the
calcium activated neutral protease,
calpain, it was hypothesized that lowering
calpain activity (by the use of an exogenous inhibitor(s)) would reduce the extent of
hypertrophy. Rats (275-300 g) were randomly assigned to either a control, beta-agonist (iso) or
cysteine protease inhibitor (
E64c) group.
Isoproterenol administration (1 mg/kg) resulted in changes for ventricular weight to
body weight ratio (increases 19%), ventricular [
RNA] (increases 105.6%), rate of pressure development (increases 22% for +dP/dt) and maximum developed left ventricular pressure (increases 19%) (p < 0.05) after 3 days.
Calpain-like activity (assessed by microplate method) increased by 45% (p < 0.05), while [cAMP] returned to control levels (following a transient rise at 1 day; 606.03 +/- 124.1 pmol/g/wet/wt to 937.9 +/- 225 (p < 0.05)).
E64c (administered 1 h prior to iso) reduced the extent of
hypertrophy, from 19 to 12%, and prevented the increases in; total [
RNA], left ventricular function, the initial [cAMP] increase and
calpain-like activity. It is concluded that a
calcium stimulated
cysteine protease(s), such as
calpain, may be involved in the biochemical and functional changes associated with
isoproterenol induced
cardiac hypertrophy.