EFFECTS OF IDRAPRIL CALCIUM ON TISSUE ANGIOTENSIN-CONVERTING ENZYME IN RATS

Tissue angiotensin-converting enzyme (ACE) inhibition was measured in rats after single intravenous (i.v.) and oral (p.o.) doses of idrapril calcium, and the correlation between peak inhibition and tissue conce ntration of the drug was investigated. Five minutes after idrapril cal cium (3 mg/kg i.v. as free acid), ACE in the examined tissues (serum, lungs, kidneys, heart, aorta, adrenals, testes, and brain) showed >50% inhibition, always associated with measurable amounts of idrapril. Af ter 90 min, ACE activity was still inhibited only in serum, lungs, kid neys, and aorta, recovering to basal values by 8 h in all samples but serum. Oral idrapril calcium (30 mg/kg) produced >50% peak ACE inhibit ion in serum, lungs, and kidneys, in which measurable levers of the dr ug were detected, and in the aorta, where idrapril was not detected. O ther tissues showed neither marked inhibition nor measurable drug leve ls. Kinetics of ACE inhibition in affected tissue mirrored those obser ved after intravenous administration. Idrapril, despite its hydrophili c nature, is able to reach extravascular tissues and to inhibit local ACE. However, in no tissue did the effect on ACE last longer than in s erum and the hypothesis of a peculiar role of tissue RAS in determinin g the hypotensive activity idrapril calcium is not supported in rats.