Cardiovascular actions and tissue-converting enzyme inhibitory effects of chronic enalapril and trandolapril treatment of spontaneously hypertensive rats.
The angiotensin I-converting enzyme (CE) inhibitors, trandolapril (RU 44570) and enalapril were administered for 2 weeks to SHR at doses (3 and 10 mg/kg/day, p.o., respectively) that produced important and comparable inhibitions of plasma (84 and 88%), aorta (97 and 88%), and atrium (89 and 82%) CE activities. At these doses, the inhibitory effects of trandolapril and enalapril were nonetheless different on CE in heart ventricle (58 and 72%) and kidney (45 and 85%). In addition, although both drugs reduced blood pressure (BP) and heart hypertrophy, trandolapril was more potent despite a lower dose-ratio. All these parameters were reexamined 1, 3, and 8 days after drug withdrawal: BP returned to control levels within 3 days in enalapril-treated rats, whereas it remained low for at least 8 days in trandolapril-treated animals. The reduction of heart hypertrophy owing to trandolapril was still present 8 days after drug discontinuation. On cessation of treatment, plasma CE increased above controls, ventricle CE returned to control levels within 3 days, whereas atrial and aortic CE activities remained inhibited for 8 days in the enalapril group. In contrast, in trandolapril-treated rats, CE activities in serum and tissues were still inhibited after 8 days. These results demonstrate that at the doses used trandolapril is more potent and longer acting than enalapril.
Chevillard
C
C
INSERM U.300, Faculté de Pharmacie, Montpellier, France.
Brown
N L
NL
Jouquey
S
S
Mathieu
M N
MN
Laliberté
F
F
Hamon
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A