Dan-Qiao Wang, Eiichi Kakizoe, Yuta Kobayashi, Keiko Shimoura and Hideki
Okunishi
Department of Pharmacology, Shimane Medical University, 89 - 1 Enya-cho,
Izumo 693 - 8501, Japan
Abstract: 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 non-significant
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.
Keywords: Aortic banding, Trandolapril, Enalapril, Collagen, Organ difference