Angiotensin converting enzyme inhibition in tissues from spontaneously hypertensive rats after treatment with captopril or MK-421
Cohen, M.L.; Kurz, K.D.
Journal of Pharmacology and Experimental Therapeutics 220(1): 63-69
1982
ISSN/ISBN: 0022-3565 PMID: 6273529 Document Number: 190201
In the spontaneously hypertensive rat, blood pressure reduction produced by inhibitors of angiotensin converting enzyme (ACE) did not correlate with inhibition of serum enzyme activity. Inhibition of ACE activity in tissues might better relate to the antihypertensive efficacy of these agents. By using hypotensive doses of 2 prototype inhibitors, captopril (10 mg/kg) and MK-421 ), no such inhibition was demonstrated with MK-421 (1.0 mg/kg p.o.). Brain ACE activity was inhibited (30-40%) at 24 h after higher doses of MK-421. At 24 h after after a single oral dose of captopril (10 mg/kg) or MK-421 (1.0 mg/kg), ACE activity returned to control values in serum, heart and brain (no apparent inhibition by MK-421). Both inhibitors produced a prolonged duration of inhibition (2-5 days) in lung, aorta and kidney. Inhibition of ACE activity appeared greatest in the aorta relative to the other tissues for both captopril and MK-421. MK-421 produced greater inhibition of renal ACE activity than did captopril. Inhibition of ACE activity in certain critical tissues may better correlate with the acute antihypertensive activity of ACE inhibitors than does inhibition of serum enzyme activity.