Abstract
The aim of the study was to ascertain whether induction of tolerance to glyceryl trinitrate (GTN) was modified by nitrosothiols. Vasodilator responses to GTN and to two nitrosothiols, namely S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-N-acetylcaptopril (SNOCAP) were measured in bovine coronary artery rings constricted with the thromboxane mimetic agent U46619. Pre-exposure of vessels to SNAP (10 microM) for 1 h resulted in cross-tolerance to GTN comparable with tolerance induced by GTN (1.0 microM). Tolerance was increased after pre-exposure to both agents. SNAP alone in lower concentrations (0.01, 0.1 and 1.0 microM) did not produce cross tolerance to GTN, but in combination with GTN (1.0 microM) caused a small but significant decrease in tolerance to GTN. This attenuating effect of SNAP on GTN tolerance was reproduced by SNOCAP (0.01 microM). We conclude that the nitrosothiols exert a biphasic effect on induction of tolerance to GTN.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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Animals
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Captopril / analogs & derivatives*
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Captopril / pharmacology
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Cattle
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Coronary Vessels / drug effects*
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Dose-Response Relationship, Drug
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Drug Tolerance
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In Vitro Techniques
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Nitroglycerin / pharmacology*
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Nitroso Compounds / pharmacology*
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Penicillamine / analogs & derivatives*
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Penicillamine / pharmacology
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Prostaglandin Endoperoxides, Synthetic / pharmacology
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S-Nitroso-N-Acetylpenicillamine
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Thromboxane A2 / analogs & derivatives
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Thromboxane A2 / pharmacology
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Vasoconstrictor Agents / pharmacology
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Vasodilation / drug effects*
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Vasodilator Agents / pharmacology*
Substances
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Nitroso Compounds
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Prostaglandin Endoperoxides, Synthetic
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Vasoconstrictor Agents
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Vasodilator Agents
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S-nitrosocaptopril
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Thromboxane A2
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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S-Nitroso-N-Acetylpenicillamine
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Captopril
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Nitroglycerin
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Penicillamine