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Title: Determinants of in vitro nitroglycerin tolerance induction and reversal: influence of dose regimen, nitrate-free period, and sulfhydryl supplementation.
Austin Authors: Henry, P J;Horowitz, J D;Louis, William J 
Affiliation: Department of Clinical Pharmacology, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Jul-1989
Publication information: Journal of Cardiovascular Pharmacology; 14(1): 31-7
Abstract: The influence of dose regimen on the induction and reversal of tolerance to nitroglycerin (NTG) is not well understood despite the current widespread clinical use of both sustained and intermittent modes of NTG administration. In an isolated coronary artery preparation both the NTG preexposure concentration and the duration of the NTG preexposure period were positive and independent determinants of the extent of NTG tolerance induction. During a "nitrate-free" or washout period, NTG tolerance was at least partially reversible. The apparent rate of NTG tolerance reversal during a "nitrate-free" period was not dependent on the absolute degree of NTG tolerance induced or on the dose regimen used to induce NTG tolerance. In this isolated vascular preparation, sulfhydryl (SH) supplementation with 1 mM N-acetylcysteine produced no significant augmentation of NTG-induced relaxations in either NTG tolerant or non tolerant tissues. N-acetylcysteine was ineffectual in attenuating the development of NTG tolerance in coronary artery preparations incubated in either Krebs bicarbonate buffer or in 10% human plasma. We conclude that in this model the NTG preexposure concentration, the duration of the NTG preexposure period, and the duration of the "nitrate-free" period are critical and independent determinants of the extent of NTG tolerance but that NTG tolerance is not significantly attenuated by SH supplementation.
Gov't Doc #: 2475712
Type: Journal Article
Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Drug Tolerance
In Vitro Techniques
Muscle Relaxation.drug effects
Nitroglycerin.administration & dosage.adverse effects.pharmacology
Prostaglandin Endoperoxides, Synthetic.pharmacology
Sulfhydryl Compounds.pharmacology
Appears in Collections:Journal articles

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