title: Biotransformation of glyceryl trinitrate by rat aortic cytochrome P450.
abstract: Denitration of glyceryl trinitrate (GTN) by the microsomal fraction of rat aorta was found to be NADPH dependent and followed apparent first-order kinetics (T1/2 70.1 min). Biotransformation of GTN was regioselective for glyceryl-1,2-dinitrate formation, and was inhibited by carbon monoxide, SKF-525A, and oxygen. In aortic microsomes prepared from phenobarbital-pretreated rats, biotransformation was increased 7-fold, and was regioselective for glyceryl-1,3-dinitrate formation. These data strongly suggest the involvement of aortic cytochrome P450 in the biotransformation of GTN.
authors.affiliation: Department of Pharmacology and Toxicology, Queen's University Kingston, Ontario, Canada.
authors.forename: B J
authors.initials: BJ
authors.lastname: McDonald
authors.forename: B M
authors.initials: BM
authors.lastname: Bennett
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology*; D001711:Biotransformation; D002248:Carbon Monoxide / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D005996:Nitroglycerin / Q000031:analogs & derivatives / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D051381:Rats
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; C014509:dinitroglycerol; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D005996:Nitroglycerin; D010100:Oxygen; D010634:Phenobarbital