Circulation, Vol 86, 1566-1574, Copyright © 1992 by American Heart Association
AT Hirsch, CE Talsness, AD Smith, H Schunkert, JR Ingelfinger and VJ Dzau
BACKGROUND. Angiotensin converting enzyme (ACE) inhibitor therapy elicits
beneficial responses from patients with heart failure. We hypothesized that
a major site of action of these drugs is tissue ACE and that ACE inhibitors
might differ in their ability to inhibit tissue ACE. To test this
hypothesis, we assessed the effects of captopril and enalapril on blood
pressure and renal function and on serum and tissue ACE activities in
sham-operated rats and rats with heart failure induced by coronary artery
ligation. METHODS AND RESULTS. During short- term (1-week) treatment,
captopril (200 mg.kg-1.day-1) and enalapril (25 mg.kg-1.day-1) elicited
equipotent effects on blood pressure and inhibition of serum ACE activity
(85%). The effects of long-term treatment (47 days) were then studied
beginning 45 +/- 5 days after coronary ligation in four treatment groups:
sham-operated, vehicle (n = 14); heart failure, vehicle (n = 10); heart
failure, captopril (n = 8); and heart failure, enalapril rats (n = 7).
During long-term treatment, captopril and enalapril caused comparable falls
of 12-18 mm Hg in blood pressure (p < 0.01 compared with vehicle
treatment). There was no change in urine volume or sodium or potassium
excretion in vehicle- or captopril-treated heart failure rats; in contrast,
enalapril-treated heart failure rats demonstrated 83% and 10% increases in
urine volume and daily sodium excretion, respectively, compared with
vehicle-treated rats (both p < or = 0.01). No significant changes in
blood urea nitrogen or creatinine were observed with either treatment.
Enalapril but not captopril elicited a significant decrease in serum and
lung ACE activities. Captopril but not enalapril inhibited aortic ACE
activity. Both agents caused a comparable inhibition of renal ACE activity.
The magnitude of inhibition of renal ACE activity but not serum and
vascular (aortic) ACE activities correlated with the long-term blood
pressure response. Enalapril but not captopril normalized renal
angiotensinogen expression; the magnitude of this effect correlated with
the increase in daily urinary sodium excretion (r = -0.43; p < or =
0.005). CONCLUSIONS. These data suggest that chronic treatment with these
two agents elicits differential effects on tissue ACE activities and renal
angiotensinogen regulation. The differential renal effects of these agents
may be important in the treatment of heart failure.
ARTICLES
Differential effects of captopril and enalapril on tissue renin- angiotensin systems in experimental heart failure
Cardiovascular Division, University of Minnesota Medical School, Minneapolis 55455.
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