Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9562
Title: Effect of acute and chronic administration of ceronapril on angiotensin converting enzyme in plasma, kidney, lung, brain regions and cerebrospinal fluid of rats.
Authors: Chen, B Z;Mendelsohn, Frederick AO
Affiliation: University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Issue Date: 1-Sep-1992
Citation: Neuropharmacology; 31(9): 929-35
Abstract: Angiotensin converting enzyme (ACE) in brain, cerebrospinal fluid (C.S.F.) and peripheral tissues was studied ex vivo after oral administration of ceronapril (SQ 29,852) to male Sprague-Dawley rats. Angiotensin converting enzyme in tissue was measured by in vitro autoradiography or enzymatic assay. In in vitro experiments, ceronapril inhibited ACE in slices of brain with an IC50 of approximately 34 nM, as measured by in vitro autoradiography. In C.S.F. ACE was inhibited with an IC50 of approximately 34 nM, as assessed by a fluorimetric enzyme assay. Ceronapril (100 mg/kg, p.o.) inhibited ACE in plasma, kidney and lung rapidly (3 hr) after administration. Inhibition of ACE in kidney lasted up to 48 hr after administration of ceronapril, whereas the activity of ACE in plasma and lung recovered rapidly (8 hr). In lung and plasma ACE was increased at 72 hr after administration. Therefore, induction of ACE in plasma and lung by the drug may partly obscure the acute inhibition and may contribute to the different time-course of inhibition of ACE from kidney. Ceronapril inhibited ACE in vascular organ of the lamina terminals (OVLT) and subfornical organ (SFO) of the brain slowly (onset at 8 hr) but persistently (from 24 to 48 hr). However the drug did not inhibit ACE in structures of the brain within the blood-brain barrier, such as the caudate-putamen, choroid plexus, globus pallidus, supraoptic nucleus and paraventricular nucleus of the hypothalamus. In C.S.F. ACE was not detectably inhibited by ceronapril but was increased at 72 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
Internal ID Number: 1331844
URI: http://ahro.austin.org.au/austinjspui/handle/1/9562
URL: http://www.ncbi.nlm.nih.gov/pubmed/1331844
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors.pharmacology
Animals
Autoradiography
Brain.drug effects.enzymology
Iodine Radioisotopes.diagnostic use
Kidney.drug effects.enzymology
Lung.drug effects.enzymology
Male
Organophosphorus Compounds.pharmacology
Peptidyl-Dipeptidase A.blood.cerebrospinal fluid.metabolism
Proline.analogs & derivatives.pharmacology
Rats
Rats, Sprague-Dawley
Appears in Collections:Journal articles

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