(Hypertension. 1996;27:176-183.)
© 1996 American Heart Association, Inc.
Articles |
ACE Inhibition Prevents and Reverses L-NAMEExacerbated Nephrosclerosis in Spontaneously Hypertensive Rats
From the Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, La.
Abstract Chronic nitric oxide inhibition exacerbates
hypertension and nephrosclerosis in spontaneously
hypertensive rats (SHRs). In this study, we determined whether
angiotensin-converting enzyme (ACE) inhibition could
prevent or reverse the systemic, renal, and glomerular
hemodynamic alterations and the pathological changes of
nephrosclerosis. Four groups of 20-week-old SHRs
were studied: group 1, untreated controls; group 2, treated with
N
-nitro-L-arginine methyl ester
(L-NAME, 50 mg/L for 3 weeks); group 3, L-NAME cotreated with quinapril
(3
mg·kg-1·d-1
for 3 weeks); and group 4, L-NAME for 3 weeks followed by quinapril for
3 weeks (same doses). The results of this study demonstrated that both
cotreatment (group 3) and posttreatment (group 4) with quinapril
reduced mean arterial pressure (186±9 and 192±9 mm Hg,
respectively, compared with group 2 SHRs, 221±5 mm Hg) and total
peripheral resistance index associated with significant
reductions in afferent and efferent arteriolar resistances;
nephrosclerosis pathological scores; and urinary
protein excretion (all at least P<.01). ACE inhibition also
significantly increased stroke index, single-nephron
glomerular filtration rate, and ultrafiltration coefficient
compared with the L-NAME SHRs. Most notable were the findings that
cotreatment with quinapril completely prevented the renal
glomerular hemodynamic alterations with
reduced glomerular capillary hydrostatic pressure and
efferent arteriolar resistance compared with both the untreated and the
L-NAME–treated SHRs (all at least P<.01). Posttreatment
with quinapril also reversed the glomerular injury
(subcapsular, -83%; juxtamedullary, -56%) and arteriolar
(-87%) injury scores obtained from renal biopsy specimens
(P<.005 and P<.0001, respectively). These
changes were associated with decreased periarteriolar fibronectin and
increased afferent arteriolar 
-smooth muscle actin deposition
(immunohistochemistry). These data, therefore, demonstrate that ACE
inhibition not only prevents but also reverses
L-NAME–exacerbated severe nephrosclerosis in
SHRs, as indicated by improved systemic, renal, and
glomerular hemodynamic changes,
proteinuria, and histological alterations.
Key Words: renal micropuncture • biopsy • L-NAME • rats, inbred, SHR • nephrosclerosis • proteinuria • angiotensin-converting enzyme inhibitors
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