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Title: Acute and chronic effects of angiotensin-converting enzyme inhibitors on tissue angiotensin-converting enzyme.
Austin Authors: Chai, Syn Y;Perich, R;Jackson, B ;Mendelsohn, Frederick AO;Johnston, Colin I
Affiliation: University of Melbourne Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 16-May-1992
Publication information: Clinical and Experimental Pharmacology & Physiology. Supplement; 19(): 7-12
Abstract: 1. The effects of angiotensin-converting enzyme (ACE) inhibitors on the tissue ACE were assessed by quantitative in vitro autoradiography after acute and chronic administrations of the drugs. 2. Following acute administration of lisinopril, perindopril or benazepril, ACE was markedly inhibited in the lung, kidney and blood vessels but not in the testis. In the brain, ACE was inhibited mainly in structures with a deficient blood brain barrier. 3. High doses of perindopril progressively inhibited ACE in other brain structures. Tissue ACE inhibition persisted after serum levels of the enzyme had returned to control levels. In the case of perindopril, the time course of tissue ACE inhibition correlated with the inhibition of the pressor responses to exogenous angiotensin I. 4. After chronic administration of lisinopril or perindopril for 14 days, a similar pattern of ACE inhibition was observed in the kidney, lung and blood vessels. In the lung, however, lisinopril was found to increase total ACE by 30%, while plasma ACE was increased two-threefold by both lisinopril and perindopril. Testicular ACE remained unaltered by chronic lisinopril treatment. 5. Overall, the changes in tissue ACE after the administration of inhibitors more closely parallel the drugs' biological effects than changes in plasma ACE or drug levels. ACE in the testis and brain is protected by permeability barriers that limit access of the drugs.
Gov't Doc #: 1327597
Journal: Clinical and Experimental Pharmacology & Physiology. Supplement
Type: Journal Article
Subjects: Administration, Oral
Angiotensin-Converting Enzyme Inhibitors.administration & dosage.pharmacology
Benzazepines.administration & dosage.pharmacokinetics
Blood Vessels.enzymology
Blood-Brain Barrier.drug effects
Dipeptides.administration & dosage.pharmacology
Indoles.administration & dosage.pharmacokinetics
Peptidyl-Dipeptidase A.blood.metabolism
Rats, Sprague-Dawley
Time Factors
Appears in Collections:Journal articles

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