Background and Purpose-Stroke-prone spontaneously hypertensive rats (S
HRSP), subjected to high NaCl intake, show severe hypertension, organ
damage, and early death. Preventive treatment with an angiotensin-conv
erting enzyme (ACE) inhibitor is known to reduce mortality. Previously
we found that proteinuria always precedes cerebral edema in SHRSP. He
nce, in this study ACE inhibition was started later, ie, directly afte
r manifestation of either proteinuria or cerebral edema. Methods-SHRSP
were subjected to 1% NaCl intake. Group 1 served as a control. In gro
up 2 early-onset treatment with the ACE inhibitor enalapril was initia
ted after proteinuria was >40 mg/d. In group 3 late-onset ACE inhibiti
on was started after the first observation of cerebral edema with T2-w
eighted MRT. Cerebral edema was expressed as the percentage of pixels
with an intensity above a defined threshold. Results-In controls media
n survival was 54 days (range, 32 to 80 days) after start of salt load
ing. 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 reduc
ed 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. SEP decreased slightly at day 7 only. Proteinuria dec
reased from 283+/-27 at day 0 to 116+/-22 mg/d at day 7 (P<0.05). Comp
lete remission of the original locus of cerebral edema was confirmed h
istologically. Conclusions-In SHRSP with proteinuria, treatment with a
n ACE inhibitor both prevented the development of cerebral edema and r
educed manifest cerebral edema and proteinuria. Survival was markedly
prolonged. These findings support the use of ACE inhibition for treatm
ent in hypertensive encephalopathy.