Effect of Time and Dose on Angiotensin Converting Enzyme during Captopril Treatment in the Rat

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Abstract
The effects of treatment time and dose of captopril with regard to angiotensin converting enzyme (ACE) in serum, lungs and kidneys of the rat were studied. Normotensive Wistar rats were treated with a constant dose of captopril (0.2 mg/ml) during various time periods. In a 2nd study rats were treated with different captopril doses (6.25, 12.5, 25, 50 and 200 .mu.g/ml water) during 3 wk. Serum ACE activity and pulmonary and kidney plasma membrane ACE concentrations were measured in both studies. Captopril treatment resulted in a rapid decrease of ACE in pulmonary and kidney plasma membranes and a simultaneous increase of serum ACE activity during the 1st day of treatment. This was followed by increased membrane concentrations of ACE in the lungs and a return to normal ACE concentrations in membranes of kidneys, presumably due to increased ACE biosynthesis. Serum ACE activity continued to increase during the whole study. Serum ACE activity increased in a dose dependent manner during treatment with different captopril doses. Increased plasma membrane ACE concentrations were not observed in the rats treated with captopril at doses below 200 .mu.g/ml water.