CHRONIC SODIUM-BALANCE AND BLOOD-PRESSURE RESPONSE TO CAPTOPRIL IN CONSCIOUS MICE

The influence of chronic administration of the converting enzyme inhib itor captopril on blood pressure and sodium balance was evaluated in c onscious Swiss Webster mice. Arterial pressure was measured with chron ic 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 demonstrat ed recovery of 100+/-3% of sodium intake under steady-state conditions (n=20 mice on 70 individual days, sodium intake range 160 to 1000 mu 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 stepwis e from 150 to 900 mu mol NaCl per day. An additional validation group (n=7) demonstrated that daily and cumulative sodium balance can be acc urately 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 mic e in which the daily sodium intake was fixed at approximate to 200 mu mol/d. This dose of captopril was determined to significantly decrease the presser response to a 10-ng bolus of angiotensin I (Ang I) from 2 4+/-5 in the control state to 6+/-2 mm Hg (n=5), After 5 days of infus ion of the converting enzyme inhibitor, mean arterial pressure signifi cantly fell from 114+/-3 to 58+/-2 mm Hg, body weight significantly de creased from 36+/-1 to 33+/-1 g, and cumulative sodium balance signifi cantly decreased to -270+/-55 mu mol. These parameters returned toward control during 5 postcontrol days. Results of this study demonstrate that accurate sodium balance measurements can be obtained from individ ual conscious mice over a 5-fold range of sodium intake. The experimen ts also indicate that converting enzyme inhibition has a potent influe nce to lower blood pressure in normal mice; the hypotensive response a ppears to be due in part to increased urinary sodium excretion.