Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/9494
Title: Differential tissue and enzyme inhibitory effects of the vasopeptidase inhibitor omapatrilat in the rat.
Austin Authors: Kubota, Eiji;Dean, Rachael G;Hubner, Richard A;Casley, David J;Johnston, Colin I;Burrell, Louise M 
Affiliation: Department of Medicine, University of Melbourne, Austin, Victoria 3084, Australia
Issue Date: 1-Sep-2003
Publication information: Clinical Science 2003; 105(3): 339-45
Abstract: Vasopeptidase inhibitors simultaneously inhibit angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The present study characterized the tissue distributions of ACE and NEP, and assessed the effects of the vasopeptidase inhibitor omapatrilat on ACE and NEP in rat tissues. In vivo ACE and NEP inhibition was studied by in vitro autoradiography and using the ACE inhibitor radioligand (125)I-MK351A and the NEP inhibitor radioligand (125)I-RB104 in rats that received oral omapatrilat (40 mg x day(-1) x kg(-1)) for 3 days. In vitro autoradiography was used to examine the distribution of ACE and NEP in the kidney, aorta, heart, adrenal gland, lung, intestine, liver, spleen and brain, and to assess enzyme inhibition after oral omapatrilat. Omapatrilat inhibited plasma ACE and increased plasma renin activity (P <0.01). Tissue ACE was inhibited by 70-95% (P <0.01), except in the brain, where ACE was not inhibited. NEP was inhibited by 87% in the kidney and by 20-40% in atria, aorta, adrenal gland, lung, liver and intestine; it was not inhibited in the brain, the ventricle or the spleen. Omapatrilat is a potent vasopeptidase inhibitor that significantly inhibits tissue ACE and NEP, with the degree of inhibition varying according to the enzyme and the tissue under assessment. The degree and site of tissue enzyme inhibition by vasopeptidase inhibitors may be relevant to end-organ protection as well as to the side-effect profiles of these agents.
Gov't Doc #: 12741953
URI: http://ahro.austin.org.au/austinjspui/handle/1/9494
DOI: 10.1042/CS20030097
URL: https://pubmed.ncbi.nlm.nih.gov/12741953
Type: Journal Article
Subjects: Administration, Oral
Adrenal Glands.enzymology
Angiotensin-Converting Enzyme Inhibitors.pharmacology
Animals
Aorta.enzymology
Autoradiography
Brain.enzymology
Heart Atria.enzymology
Intestines.enzymology
Iodine Radioisotopes.diagnostic use
Kidney.enzymology
Liver.enzymology
Lung.enzymology
Male
Neprilysin.analysis.antagonists & inhibitors
Peptidyl-Dipeptidase A.analysis.blood
Pyridines.pharmacology
Rats
Rats, Sprague-Dawley
Renin.blood
Thiazepines.pharmacology
Appears in Collections:Journal articles

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