To determine the renoprotective effects of a
calcium antagonist (
felodipine) and an
angiotensin-converting enzyme (
ACE) inhibitor (
enalapril), alone or in combination, 10 groups of 19-week-old spontaneously hypertensive rats (SHR) (with or without
N(G)-nitro-L-arginine methyl ester [
L-NAME]) were studied using renal
micropuncture techniques. Group 1 (control), group 2 (
felodipine, 30 mg x kg(-1) x d[-1]), group 3 (
enalapril, 30 mg x kg(-1) x d[-1]), and group 4 (
felodipine plus
enalapril, 15 mg x kg(-1) x d(-1) each agent) were studied after 3 weeks of treatment without
L-NAME.
L-NAME (50 mg/L) cotreatment was administered in
drinking water to groups 6 through 10 using the same doses of each agent as in groups 1 through 4: group 5 (only
L-NAME), group 6 (
felodipine), group 7 (
enalapril), and group 8 (
felodipine plus
enalapril). Groups 9 and 10 received
L-NAME initially for 3 weeks followed by
felodipine or
felodipine plus
enalapril, respectively, for the subsequent 3 weeks. All three treatments resulted in reductions in mean arterial pressure and total peripheral vascular resistance (P<.001) that were associated with important structural and functional renal microcirculatory improvements. Thus, the pathological
nephrosclerosis (subcapsular and juxtamedullary) glomerular and arteriolar injury scores were improved (P<.05 at least) in association with normalization of afferent and efferent arteriolar resistances, and single-nephron glomerular filtration rate, plasma flow, and blood flow were significantly improved, as well as the ultrafiltration coefficient (compared with group 5,
L-NAME). Thus, the
calcium antagonist
felodipine, alone or in combination with an
ACE inhibitor, not only prevented but also reversed
L-NAME-exacerbated hypertensive
nephrosclerosis in SHR.