Cardiac dysfunction in animals with
congestive heart failure due to
myocardial infarction (MI) is known to be associated with a wide variety of defects in receptor and post-receptor mechanisms. Since the heart function have been shown to be improved by treatment with different
angiotensin converting enzyme (
ACE) inhibitors, we examined the effects of
imidapril, an
ACE inhibitor, on changes in post-receptor mechanisms involving
adenylyl cyclase (AC) and
G proteins in the failing heart.
Heart failure in rats was induced by occluding the coronary artery and 3 weeks later the animals were treated daily with 1 mg/kg (orally)
imidapril for 5 weeks. The animals were assessed for their left ventricular function and crude membranes were isolated from the viable left ventricle and examined for AC activities as well as
G-protein activities and expression. Animals with
heart failure exhibited depressions in ventricular function and AC activities in the absence or presence of
forskolin, NaF and
Gpp(NH)p. The AC activity in the presence of
pertussis toxin was increased whereas that in the presence of
cholera toxin was decreased in the failing heart.
Protein contents and
mRNA levels for G(i)-
proteins were increased whereas those for G(s)-
proteins were unaltered in the infarcted heart. All these changes due to MI were prevented by
imidapril treatment. The results indicate that the depressed cardiac function in the failing heart may partly be due to the direct effects of changes in AC and G(i)
proteins.