Effects of combination therapy with enalapril and losartan on the rate of progression of renal injury in rats with 5/6 renal mass ablation.

Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (AT1RA) slow the rate of progression of experimental renal disease. Although the end result of both classes of drugs is to block the renin-angiotensin system (RAS), ACE! and AT1RA act at different sites in the RAS cascade. The aim of this study was to compare the effects of an ACEI (enalapril) and AT1RA (losartan), alone or in combination, in slowing the progression of experimental renal disease in a model of reduced renal mass. Two weeks after 5/6 renal ablation, rats were divided into five groups matched for body weight, systolic BP (SBP), and urinary protein excretion rate (UprotV). The effects on SBP and UprotV of treatment with 25 and 40 mgIL enalapril (groups I and II; both n = 7), 180 mg/L losartan (group III, n = 8), or a combination of enalapril (25 mg/L) + losartan (180 mgIL) (group IV, n = 9) versus vehicle (group V, n 9) were studied for 12 wk. Remnant kidneys were then assessed histologically for evi- dence of focal and segmental glomerubosclerosis and hyalino- sis (FSGS), and interstitial fibrosis. There were no significant differences (NSD) in body weight among the groups at any time. Combination therapy reduced SBP (122 ± 8 mmHg) significantly at 12 wk to levels similar to losartan (127 ± 3 mmHg) or enalapril (40 mgIL) alone ( 124 ± 5 mmHg) (P < 0.05 versus vehicle controls). With equivalent antihypertensive effects, no differences in frequency of FSGS were discerned among the treatment groups (groups II through IV; F = 1.7, NSD). Tububointerstitial injury scores followed a similar pat- tern. BP was highly correlated with the extent of FSGS, both among individual rats (r = 0.68, P = 0.05) and the group means (r = 0.99, P 0.001). We conclude that the renopro- tective effects of enalapril, losartan, or combination therapy are similar in this model over the 12 wk of the study, and are closely related to the magnitude of their antihypertensive