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MECHANISM OF TOLERANCE DEVELOPMENT TO ORGANIC NITRATES
Abstract
Tolerance to the vasodilator activity of organic nitrates appears to involve an alteration in a receptor in vascular smooth muscle. An in vitro model of nitrate tolerance was developed by incubation of rabbit thoracic aorta with organic nitrate at alkaline pH, producing a time- and concentration-dependent decrease in sensitivity to glyceryl trinitrate. Cross-tolerance is observed to all organic nitrates studied but not to nonnitrate vasodilators. When aortic strips are incubated at alkaline pH, nitrite formation is enhanced and tissue SH levels decrease. It s proposed that organic nitrate tolerance involves the oxidation of a critical sulfhydryl in the glyceryl trinitrate "receptor." This hypothesis is supported by the reversal of both in vitro - and in vivo -induced glyceryl trinitrate tolerance by the disulfide reducing agent, dithiothreitol.
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Cited by
Nitric oxide donors: chemical activities and biological applications
Wang, P. G., Xian, M., Tang, X., Wu, X., Wen, Z., Cai, T., & Janczuk, A. J. (2002) · Chemical Reviews · doi:10.1021/cr000040l · Cited by 1,337
Biosynthesis and Metabolism of Endothelium-Derived Nitric Oxide
Ignarro, L. J. (1990) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.30.040190.002535 · Cited by 1,314
Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors
Mollace, V., Muscoli, C., Masini, E., Cuzzocrea, S., & Salvemini, D. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.2.1 · Cited by 357
Leier, C. V., Huss, P., Magorien, R. D., & Unverferth, D. V. (1983) · Circulation · doi:10.1161/01.cir.67.4.817 · Cited by 289
Tolerance to the Organic Nitrates: New Ideas, New Mechanisms, Continued Mystery
Parker, J. D., & Gori, T. (2001) · Circulation · doi:10.1161/circ.104.19.2263 · Cited by 21
Metadata
- Authors
- NEEDLEMAN, P., & JOHNSON, E. M.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1973-03
- Volume
- 184
- Issue
- 3
- Pages
- 709-715
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2214008998
- Cited by
- 495
- References
- 0
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- closed
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- NEEDLEMAN, P., & JOHNSON, E. M. (1973). MECHANISM OF TOLERANCE DEVELOPMENT TO ORGANIC NITRATES. The Journal of Pharmacology and Experimental Therapeutics. https://doi.org/10.1016/s0022-3565(25)29462-9
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
