From the Departments of Nephrology (E.L.A.B., H.A.K., J.A.J.), Neurology
(P.R.D.B.), and Pathology (R.G., G.H.J.), University Hospital Utrecht, and
Department of In Vivo Nuclear Magnetic Resonance, Bijvoet Center, Utrecht
University (E.L.A.B., K.N.) (Netherlands).
Background and Purpose—Stroke-prone
spontaneously hypertensive rats (SHRSP), subjected to high NaCl intake,
show severe hypertension, organ damage, and early death. Preventive
treatment with an angiotensin-converting enzyme (ACE)
inhibitor is known to reduce mortality. Previously we found
that proteinuria always precedes cerebral edema in SHRSP. Hence, in
this study ACE inhibition was started later, ie, directly after
manifestation of either proteinuria or cerebral edema.
Methods—SHRSP were subjected to 1% NaCl intake. Group 1 served
as a control. In group 2 early-onset treatment with the ACE
inhibitor enalapril was initiated after proteinuria was
>40 mg/d. In group 3 late-onset ACE inhibition was started after the
first observation of cerebral edema with T2-weighted MRI. Cerebral
edema was expressed as the percentage of pixels with an intensity above
a defined threshold.
Results—In controls median survival was 54 days (range, 32
to 80 days) after start of salt loading. The terminal level of cerebral
edema was 19.0±3.0%. Under early-onset enalapril, median survival
increased to 320 days (range, 134 to 368 days; P<0.01
versus group 1). Cerebral edema was prevented in all but 1 rat.
Systolic blood pressure was slightly and transiently reduced at
day 14. Proteinuria was markedly reduced (52±7 versus 190±46 mg/d in
group 1 at day 7; P<0.05). Under late-onset enalapril,
median survival was 264 days (range, 154 to 319 days;
P<0.01 versus group 1). Cerebral edema decreased to
baseline levels (9.6±2.9 at day 0 to 3.4±0.5% at day 3;
(P<0.05). Ultimately cerebral edema reoccurred in 6 of
the 8 rats. SBP decreased slightly at day 7 only. Proteinuria decreased
from 283±27 at day 0 to 116±22 mg/d at day 7
(P<0.05). Complete remission of the original locus of
cerebral edema was confirmed histologically.
Conclusions—In SHRSP with proteinuria, treatment with an ACE
inhibitor both prevented the development of cerebral edema
and reduced manifest cerebral edema and proteinuria. Survival was
markedly prolonged. These findings support the use of ACE inhibition
for treatment in hypertensive encephalopathy.
Department
of Internal Medicine,
Cardiovascular Division,
University of Iowa College of Medicine,
Iowa City, Iowa
© 1998 American Heart Association, Inc.
Original Contributions
Enalapril Prevents Imminent and Reduces Manifest Cerebral Edema in Stroke-Prone Hypertensive Rats
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