Effects of subchronic treatment with trandolapril and enalapril on cardiovascular morphologic alterations in the aged spontaneously hypertensive rat with heart failure.
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)
Secchi
J
J
Centre de Recherches Roussel UCLAF, Romainville, France.
Lecaque
D
D
Dunn
F W
FW
Jouquey
S
S
Auberval
U D
UD
Benzoni
F
F
Sirugue
O
O
Hamon
G
G
D000375:Aging; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy*; D004656:Enalapril / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy / Q000473:pathology*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology*; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A