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|Title:||Blockade of angiotensin converting enzyme in circumventricular organs of the brain after oral lisinopril administration demonstrated by quantitative in vitro autoradiography.|
|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.|
|Citation:||Clinical and Experimental Pharmacology & Physiology; 14(3): 155-8|
|Abstract:||1. To elucidate the central effect of lisinopril, a new angiotensin converting enzyme (ACE) inhibitor, ACE localization and levels were followed in the brain of Sprague-Dawley rats by quantitative in vitro autoradiography after administration of the drug. 2. Following acute lisinopril (10 mg/kg p.o.) treatment, serum ACE activity was acutely reduced, but returned to normal by 24 h. 3. Levels of ACE in most parts of the brain, including the basal ganglia and choroid plexus of all ventricles were not affected by lisinopril. Lisinopril inhibited brain ACE in the subfornical organ and organum vasculosum of the lamina terminalis, circumventricular organs, where the blood brain barrier is deficient. These regions are rich in ACE and angiotensin II receptors, and are known targets for angiotensin II-induced effects on fluid, electrolyte and blood pressure homeostasis. 4. These observations indicate that quantitative in vitro autoradiography is a powerful method to study the access of drugs to the central nervous system. 5. This study shows that blood brain barrier plays an important role in limiting the penetration of lisinopril into the central nervous system. The circumventricular organs may be important targets for ACE inhibitors.|
|Internal ID Number:||2822304|
|Subjects:||Angiotensin-Converting Enzyme Inhibitors.pharmacology|
Enalapril.analogs & derivatives.pharmacology
Rats, Inbred Strains
|Appears in Collections:||Journal articles|
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