Differential suppression of pressure-overload cardiac and aortic hypertrophy in rats by angiotensin-converting enzyme inhibitors.
Role of tissue angiotensin-converting enzyme (ACE) in the development of pressure-overload cardiovascular hypertrophy was examined in rats by comparing the inhibitory effect of trandolapril (high efficiency on tissue ACE) with that of enalapril (low efficiency) at equally antihypertensive doses. Rats with abdominal aorta banded or sham-operated were orally treated with trandolapril (0.5 mg/kg per day), enalapril (20 mg/kg per day) or vehicle for 8 weeks after the surgical maneuvers. In vehicle-treated rats, the banding raised the intra-aortic systolic pressure by 58%, diastolic pressure by 31%, maximum velocity of pressure rise by 65%, left ventricular (LV) weight by 41%, LV hydroxyproline concentration by 56%, aortic mass by 46%, LV ACE activity by 45%, and aortic ACE activity by 265%. Although both drugs equally reduced the aortic systolic pressure to approx. 70% and diastolic pressure to approx. 80% that of banded rats receiving vehicle, trandolapril partially prevented the LV hypertrophy, whereas enalapril yielded nonsignificant suppression. Trandolapril completely prevented the LV increments in hydroxyproline and ACE activity, whereas enalapril partially inhibited the LV hydroxyproline increase with little inhibition of LV ACE activity. In contrast, both inhibitors almost completely prevented the aortic hypertrophy, with the ACE activity of the aorta being potently inhibited. These results suggest that tissue ACE is the principal factor for pressure-induced aortic hypertrophy and an important yet non-essential factor for LV hypertrophy.
Wang
D Q
DQ
Department of Pharmacology, Shimane Medical University, Izumo, Japan.
Kakizoe
E
E
Kobayashi
Y
Y
Shimoura
K
K
Okunishi
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000473:pathology; D001018:Aortic Diseases / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects*; D006332:Cardiomegaly / Q000473:pathology / Q000517:prevention & control*; D004656:Enalapril / Q000494:pharmacology; D006352:Heart Ventricles / Q000473:pathology; D006909:Hydroxyproline / Q000097:blood; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril; D004656:Enalapril; D006909:Hydroxyproline