Induction of angiotensin-converting enzyme with the ACE inhibitory compound MK-421 in rat lung

Having observed that treatment of rats with captopril led to an increased ACE activity in serum and ACE concentration in lungs, we treated female Wistar Kyoto rats for 7 days with the esterified ACE inhibitor, MK-421 (1.0 mg/kg body weight per day), administered by Alzet osmotic minipump. Serum ACE activity decreased by 67% during MK-421 treatment when measured in non-dialyzed serum samples. Removal of the drug by dialysis unmasked a 280% increase of serum ACE activity. ACE concentration of crude lung homogenate increased 134% in MK-421-treated rats and ACE concentration in purified pulmonary plasma membranes increased by 34%. The increase of serum and lung ACE in MK-421-treated rats was similar to that seen in rats treated with captopril, and was probably due to induction of ACE biosynthesis. The mechanisms of this induction are unknown.