Inhibition of angiotensin-converting enzyme (ACE) in plasma and tissue.
Inhibition of angiotensin-converting enzyme (ACE) in rat plasma and tissue was studied after administration of quinapril, a new orally active ACE inhibitor with an intermediate duration of action. Tissue and plasma ACE was assessed by a radioinhibitor-binding assay and by in vitro autoradiography using [125I]351A as the radioligand. Individual tissues in rats were differentially inhibited in time and degree. The highest ACE inhibition in plasma and in tissues occurred within the first 2 h after gavage treatment with quinapril, 0.3 mg/kg. After 24 h, ACE was still inhibited by 25% in plasma, by 30% in the aorta, by 35% in the kidneys, and by more than 40% in cardiac atria and ventricles. Plasma and kidney tissues showed increasing ACE inhibition in a dose-dependent manner after oral dosing with quinapril. In the brain, only the structures outside the blood-brain barrier were inhibited after the administration of 0.1 mg/kg of quinapril. Similarly, testicular ACE was unaffected by quinapril. These results demonstrate a prolonged effect of quinapril on tissue ACE and suggest that ACE inhibition in the heart, vasculature, and kidneys may be of particular importance in pathologic states such as hypertension or heart failure.
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Australia.
B
B
Fabris
B Z
BZ
Chen
V
V
Pupic
R
R
Perich
C I
CI
Johnston
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007546:Isoquinolines / Q000097:blood / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D000077583:Quinapril; D051381:Rats; D011919:Rats, Inbred Strains; D044005:Tetrahydroisoquinolines; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077583:Quinapril