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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aorta / enzymology*
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Biotransformation
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Carbon Monoxide / pharmacology
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Cytochrome P-450 Enzyme Inhibitors
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Cytochrome P-450 Enzyme System / biosynthesis*
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Enzyme Induction / drug effects
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Kinetics
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Microsomes / enzymology
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Microsomes, Liver / enzymology
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Nitroglycerin / analogs & derivatives
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Nitroglycerin / metabolism*
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Oxygen / pharmacology
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Phenobarbital / pharmacology
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Proadifen / pharmacology
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Rats
Substances
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Cytochrome P-450 Enzyme Inhibitors
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dinitroglycerol
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Carbon Monoxide
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Cytochrome P-450 Enzyme System
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Proadifen
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Nitroglycerin
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Oxygen
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Phenobarbital