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From the Alton Ochsner Medical Foundation, New Orleans, La.
Correspondence to Edward D. Frohlich, MD, Vice President for Academic Affairs, Alton Ochsner Medical Foundation, 1516 Jefferson Hwy, New Orleans, LA 70121.
Abstract—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
NG-nitro-L-arginine methyl ester
[L-NAME]) were studied using renal micropuncture techniques. Group 1
(control), group 2 (felodipine, 30 mg · kg-1
· d-1), group 3 (enalapril, 30 mg ·
kg-1 · d-1), and group 4 (felodipine
plus enalapril, 15 mg · kg-1 ·
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.
© 1998 American Heart Association, Inc.
Scientific Contributions
Renoprotective Effects of Felodipine and/or Enalapril in Spontaneously Hypertensive Rats With and Without L-NAME
Key Words: nephrosclerosis • nitric oxide synthase • renoprotection • renal pathological changes • glomerular filtration rate • arteriolar injury • rats, inbred SHR
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