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Title: Inhibition of tissue angiotensin converting enzyme. Quantitation by autoradiography.
Austin Authors: Sakaguchi, K;Chai, Syn Y;Jackson, B ;Johnston, Colin I;Mendelsohn, Frederick AO
Affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Mar-1988
Publication information: Hypertension; 11(3): 230-8
Abstract: Inhibition of angiotensin converting enzyme (ACE) in serum and tissues of rats was studied after administration of lisinopril, an ACE inhibitor. Tissue ACE was assessed by quantitative in vitro autoradiography using the ACE inhibitor [125I]351A, as a ligand, and serum ACE was measured by a fluorimetric method. Following oral administration of lisinopril (10 mg/kg), serum ACE activity was acutely reduced but recovered gradually over 24 hours. Four hours after lisinopril administration, ACE activity was markedly inhibited in kidney (11% of control level), adrenal (8%), duodenum (8%), and lung (33%; p less than 0.05). In contrast, ACE in testis was little altered by lisinopril (96%). In brain, ACE activity was markedly reduced 4 hours after lisinopril administration in the circumventricular organs, including the subfornical organ (16-22%) and organum vasculosum of the lamina terminalis (7%; p less than 0.05). In other areas of the brain, including the choroid plexus and caudate putamen, ACE activity was unchanged. Twenty-four hours after administration, ACE activity in peripheral tissues and the circumventricular organs of the brain had only partially recovered toward control levels, as it was still below 50% of control activity levels. These results establish that lisinopril has differential effects on inhibiting ACE in different tissues and suggest that the prolonged tissue ACE inhibition after a single oral dose of lisinopril may reflect targets involved in the hypotensive action of ACE inhibitors.
Gov't Doc #: 2832327
Journal: Hypertension
Type: Journal Article
Subjects: Adrenal Glands.enzymology
Angiotensin-Converting Enzyme Inhibitors.pharmacology
Dipeptides.diagnostic use
Enalapril.analogs & derivatives.pharmacology
Iodine Radioisotopes.diagnostic use
Peptidyl-Dipeptidase A.analysis
Rats, Inbred Strains
Renin-Angiotensin System.drug effects
Time Factors
Appears in Collections:Journal articles

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