Biotransformation of glyceryl trinitrate by rat aortic cytochrome P450.
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.
McDonald
B J
BJ
Department of Pharmacology and Toxicology, Queen's University Kingston, Ontario, Canada.
Bennett
B M
BM
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
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