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|Title:||Inhibition of angiotensin converting enzyme (ACE) in plasma and tissues: studies ex vivo after administration of ACE inhibitors.|
|Authors:||Johnston, Colin I;Mendelsohn, Frederick AO;Cubela, R B;Jackson, B;Kohzuki, M;Fabris, Bruno|
|Affiliation:||University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.|
|Citation:||Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension; 6(3): S17-22|
|Abstract:||Two methods of radio-inhibitor binding to tissue membrane homogenates and in vitro autoradiography have been used for ex vivo studies on the inhibition of tissue angiotensin converting enzyme (ACE) following acute and chronic administration of ACE inhibitors. Tissue ACE is differentially inhibited in time and degree in different tissues of the rat. Plasma and kidney ACE are inhibited completely at low doses whereas lung and aorta are only inhibited by 60-70%, even after very high does of ACE inhibitors. In the brain only those structures outside the blood-brain barrier are inhibited at low doses but at high doses perindopril appears able to cross the blood-brain barrier. Similarly, testicular ACE is not inhibited and appears to be protected by a blood-testis barrier. Preliminary results suggest that after chronic administration there is also a variable pattern of induction and inhibition of ACE in different tissues. By relating the degree of tissue inhibition to physiological responses it may be possible to determine the role of local renin-angiotensin systems in regional haemodynamics and in the hypotensive action of ACE inhibitors. Further, the techniques of radioligand inhibitor binding and in vitro autoradiography can be extended to other important cardiovascular enzymes (renin and kallikrein) when suitable high affinity specific inhibitors become available.|
|Internal ID Number:||2852234|
|Subjects:||Angiotensin-Converting Enzyme Inhibitors.administration & dosage.pharmacology|
In Vitro Techniques
Indoles.administration & dosage.pharmacology
|Appears in Collections:||Journal articles|
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