42 female rats (230–260 g) made hypertensive by bilateral renal encapsulation with latex envelopes were divided into three equal groups. Two groups were administered the angiotensin-converting enzyme inhibitor captopril (SQ 14,225) in drinking water at a concentration sufficient to yield a dose of 25 and 50 mg/kg/day, respectively. The third group was untreated. A fourth group (14 rats) served as a normotensive control group. Systolic blood pressures and body weights were measured weekly during a 4-week control and an 8-week experimental period. Both doses prevented the elevation of blood pressure to the level of the untreated hypertensive controls. Blood pressure of the group receiving the higher dose of captopril was within the range of that of the normotensive control group by the end of the experiment while that of the group receiving the lower dose was between the blood pressures of untreated hypertensive and normotensive controls. Renal encapsulation resulted in failure of the rats to grow normally. Administration of captopril at either dose had no additional effect on body weight. To test whether inhibition of the angiotensin-converting enzyme occurred at the doses of captopril used, angiotensin I (200 µg/kg s.c.) and bradykinin (200 µg/kg s.c.) were administered separately and their effects on water intakes of control and captopril-treated groups tested. Captopril inhibited the drinking response to angiotensin I while increasing it in response to bradykinin. The pressor response following intravenous administration of 1.25 µg angiotensin I/kg to anesthetized rats was also studied. The groups treated with captopril had a significantly reduced response to angiotensin I compared with those of either normotensive or hypertensive groups. The results of the three tests suggest that inhibition of the angiotensin-converting enzyme occurred at both doses of captopril, with the higher dose inducing a somewhat greater inhibition. At autopsy, heart weight of the group receiving the higher dose of captopril was significantly less than that of the untreated hypertensive group, but significantly greater than that of the normotensive group. These results also suggest that captopril, at the doses used, provided significant protection against elevation of blood pressure in renal hypertensive rats.

Keywords:
Hypertension, Captopril, Angiotensin I, Bradikinin, Water intake, Heart weight
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© 1981 S. Karger AG, Basel
1981
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