Chronic Sodium Balance and Blood Pressure Response to Captopril in Conscious Mice

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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 [micro sign]mol/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 [micro sign]mol 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 [middle dot] kg (-1) [middle dot] d-1). Experiments were then performed to examine the influence of intravenous captopril infusion (40 mg [middle dot] kg-1 [middle dot] d-1, n=7) in mice in which the daily sodium intake was fixed at [almost equal to]200 [micro sign]mol/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 [micro sign]mol. 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. (Hypertension. 1998;32:923-928.)

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