The effects of a 3-month treatment period with the
angiotensin-converting enzyme (
ACE) inhibitors trandolapril (0.3 mg/kg/day, p.o.) and
enalapril (10 mg/kg/day, p.o.) on hemodynamics,
cardiac hypertrophy, and vascular structures were examined in old spontaneously hypertensive rats (SHRs) (24 months at the end of treatment) presenting with
congestive heart failure. During the course of treatment, the mortality rate was lower in the two treated groups than in the control group. At the end of treatment, serum ACE activity was inhibited by 63 and 33% by
trandolapril and
enalapril, respectively, but the decrease in blood pressure they induced was not significant. The
atrial natriuretic factor(
ANF) plasma levels and
cyclic GMP urine excretion were about 10-fold and 3-fold higher, respectively, in old SHRs than in old Wistar rats. These values were markedly decreased by both
ACE inhibitors. The ventricular
hypertrophy was greatly decreased by both compounds (-24% by
trandolapril and -26% by
enalapril). In the aorta, the media
hypertrophy was significantly decreased and nuclear density increased to a similar extent by both
ACE inhibitors. In the mesenteric artery,
trandolapril treatment induced a complete regression of the media
hypertrophy and a marked decrease in extracellular matrix surface. In addition, the
collagen network appeared less dissociated in the treated animals. Similarly the nuclear density was increased and the surface of cell nuclei was decreased by
trandolapril.
Enalapril appeared much less potent on these parameters. These data demonstrate that treatment with
trandolapril of aged SHRs presenting with
heart failure results in an increase in survival of the animals and a marked regression of cardiac and vascular
hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)