The potent converting
enzyme inhibitor (CEI)
SQ14,225, which is known to prevent the formation of
angiotensin II (AII) has been used to evaluate the role of AII in the development and reversal of
cardiac hypertrophy. The present study describes the effect of CEI on blood pressure (BP) and myocardial
hypertrophy (prevention and reversal) in the spontaneously hypertensive rat (SHR). A group of 3-week- and 8-week-old male SHR was treated with CEI (30 mg/kg in
drinking water) for 6 weeks. An additional group of SHR was also treated with a combination of CEI and a
diuretic (
hydrochlorothiazide, 500 mg/liter). Heart weight, BP,
deoxyribonucleic acid (
DNA),
ribonucleic acid (
RNA),
hydroxyproline, myocardial
catecholamines, and plasma
renin activity (PRA) were determined. In the prevention study, we found a significant reduction in the ratio of heart weight to
body weight along with the prevention of
hypertension (200 vs 145 mm Hg, p less than 0.001). Similar reductions in BP and heart weights were obtained with the reversal group. A better BP control was noted in the CEI and
hydrochlorothiazide group. The reduction of heart weight was associated with a reduction in
RNA and
hydroxyproline content. In all groups, we found a significant increase in PRA (p less than 0.001) and a slight increase in tissue
catecholamine concentration. No change in kidney weight was found in any group. Data clearly showed that
oral administration of CEI prevented and reversed
cardiac hypertrophy in SHR. Reversal was associated with a decrease in myocardial
collagen content. These data indicate that prevention of AII formation in combination with BP control can prevent and reverse
cardiac hypertrophy in SHR. Of course, whether or not CEI acts only through the
renin angiotension system is still speculative.