Effects of an Angiotensin-Converting Enzyme (ACE) Inhibitor, SA446, on Tissue ACE Activity in Normotensive, Spontaneously Hypertensive, and Renal Hypertensive Rats

Abstract

Effects of an angiotensin-converting enzyme (ACE) inhibitor, SA446, on the renin-angiotensin system, particularly on tissue ACE activity, were studied in Wistar-Kyoto normotensive rats (WKY), spontaneously hypertensive rats (SHR), and two-kidney, one-clip renal hypertensive rats (RHR) by repeated oral administration for 7 days. SA446 (45 mg/kg/day p.o.) inhibited ACE activity in the lung, brain, kidney, heart, and whole blood throughout the administration period in WKY, but showed a slight hypotensive action and no inhibition of aorta ACE activity. On the other hand, SA446 had an apparent hypotensive action at the same dose in SHR and inhibited ACE activity significantly in the aorta as well as the kidney and whole blood during the administration period. Furthermore, enzyme activity in the aorta, kidney, heart, and whole blood was also inhibited at a hypotensive dose of SA446 (10 mg/kg/day p.o.) in RHR. The inhibition in whole blood and kidney was almost complete, and the inhibition in the aorta was greater on day 7 than on day 1. The maximum decrease of blood pressure was correlated with the maximum inhibition in aorta ACE activity, but not in brain, lung, or heart ACE activity. In addition, a good positive correlation was observed between the basal blood pressure and the basal aorta ACE activity in WKY, SHR, and RHR, although there was no correlation in the brain, lung, kidney, heart, or whole blood. These results suggest that the antihypertensive action of SA446 by repeated administration may be due to inhibition of arterial ACE activity in addition to inhibition of plasma and kidney ACE activity.(ABSTRACT TRUNCATED AT 250 WORDS)