(Hypertension. 1998;32:923-928.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
Chronic Sodium Balance and Blood Pressure Response to Captopril in Conscious Mice
From the Department of Physiology, Medical College of Wisconsin, Milwaukee, Wis.
Correspondence to Dr David L. Mattson, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. E-mail dmattson{at}mcw.edu
Abstract—The influence of
chronic administration of the converting enzyme inhibitor
captopril on blood pressure and sodium balance was evaluated in
conscious Swiss Webster mice. Arterial pressure was
measured with chronic indwelling catheters, and sodium balance was
determined by infusing sodium intravenously in isotonic
saline and collecting urine 24 h/d. Experiments to validate sodium
balance measurements in mice demonstrated recovery of 100±3% of
sodium intake under steady-state conditions (n=20 mice on 70 individual
days, sodium intake range 160 to 1000 µmol/d). It was further
demonstrated that mean arterial pressure, heart rate, and
body weight were unaltered from 115±7 mm Hg, 646±12 bpm, and
34±0.6 g, respectively, as sodium intake was increased stepwise from
150 to 900 µmol NaCl per day. An additional validation group
(n=7) demonstrated that daily and cumulative sodium balance can be
accurately determined during and after the intravenous
administration of an agent known to alter renal sodium handling
(furosemide 50 mg · kg-1 ·
d-1). Experiments were then performed to examine the
influence of intravenous captopril infusion (40 mg ·
kg-1 · d-1, n=7) in mice in which the
daily sodium intake was fixed at 
200 µmol/d. This dose of
captopril was determined to significantly decrease the pressor response
to a 10-ng bolus of angiotensin I (Ang I) from 24±5 in the
control state to 6±2 mm Hg (n=5). After 5 days of infusion of
the converting enzyme inhibitor, mean arterial
pressure significantly fell from 114±3 to 58±2 mm Hg, body
weight significantly decreased from 36±1 to 33±1 g, and cumulative
sodium balance significantly decreased to -270±55 µmol. These
parameters returned toward control during 5 postcontrol
days. Results of this study demonstrate that accurate sodium balance
measurements can be obtained from individual conscious mice over a
5-fold range of sodium intake. The experiments also indicate that
converting enzyme inhibition has a potent influence to lower blood
pressure in normal mice; the hypotensive response appears to be due in
part to increased urinary sodium excretion.
Key Words: renin-angiotensin system • captopril • blood pressure • sodium
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