From the Departments of Nephrology (E.L.A.B., M.S., H.A.K., J.A.J.) and
Experimental Neurology (P.R.D.B.), and Pathology (G.H.J.), University Hospital
Utrecht, and Department of In Vivo NMR, Bijvoet Center, Utrecht University
(E.L.A.B., K.N.), Utrecht, the Netherlands.
Correspondence and reprint requests to Jaap A. Joles DVM, PhD, Department of Nephrology and Hypertension (F03.226), Utrecht University Hospital, PO Box 85500, 3508 GA Utrecht, Netherlands. E-mail nephrology.gdl{at}pobox.ruu.nl
Background and Purpose—Stroke-prone
spontaneously hypertensive rats (SHRSP) subjected to high sodium intake
develop severe hypertension, cerebral edema, and proteinuria,
culminating in organ damage and early death. MRI, which can be applied
serially, provides the unique opportunity to study temporal and
quantitative relations between these changes and whether diminution of
sodium intake can attenuate established cerebral edema.
Methods—SHRSP were subjected to 1% NaCl in drinking water.
Cerebral MRI, proteinuria and systolic blood pressure (SBP)
were measured serially. After detection of cerebral edema (T2-weighted
MRI), 6 rats were killed for histology, to confirm the diagnosis of
cerebral edema. The others were followed up for 7 more days while salt
loading was continued (n=10, group 1) or after sodium intake was
normalized (n=7, group 2).
Results—SHRSP invariably developed cerebral edema in 30 days
(range, 8 to 54 days). At this point neurological signs were absent in
16 of 23 rats. SBP rose until 1 week before detection of cerebral
edema, and then stabilized at approximately 265 mm Hg.
Proteinuria invariably preceded cerebral edema, with a concentration
exceeding 40 mg/d predicting development of cerebral edema in 9 days
(range, 3 to 15 days). There was linear correlation
(R=.62, P<.0001) between proteinuria and
cerebral edema (pixels with an intensity above a defined threshold).
Rats in group 1 showed an increase in cerebral edema (from 5.8±1.1%
to 12.5±2.8%; P<.05), and proteinuria remained high
(from 305±44 to 338±29 mg/d); and 2 died spontaneously. Rats in group
2 showed no significant change in edema (from 4.9±0.5% to 6.9±1.3%)
but a marked fall in proteinuria (from 294±24 to 119±10 mg/d;
P<.05), both significantly different from group 1
(P<.05); all survived. SBP remained unaltered in both
groups.
Conclusions—Our data establish MRI as a sensitive method for
detection of cerebral edema, often prior to neurological signs, in
SHRSP. Proteinuria predicts cerebral edema, and these two
variables, both obtained noninvasively, are quantitatively related.
Moreover, in SHRSP normalizing sodium intake after salt loading
attenuates development of cerebral edema and reduces proteinuria.
Department
of Physiology and Biophysics,
University of Nebraska Medical Center,
Omaha, Nebraska
© 1998 American Heart Association, Inc.
Original Contributions
Proteinuria Precedes Cerebral Edema in Stroke-Prone Rats
A Magnetic Resonance Imaging Study
Editorial Comment
A Magnetic Resonance Imaging Study
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