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Nitrate tolerance and the links with endothelial dysfunction and oxidative stress
Katherine E Fayers1, Michael H Cummings, Kenneth M Shaw
1Academic Department of Diabetes and Endocrinology, Queen Alexandra Hospital, Southwick Road, Cosham, Portsmouth, Hants, PO6 3LY, UK. katefayers@hotmail.com
British Journal of Clinical Pharmacology
|November 18, 2003
Summary
Nitric oxide (NO) is key to blood vessel relaxation. Oxidative stress contributes to tolerance to organic nitrate drugs, potentially linking to primary NO resistance.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Biochemistry
Background:
- Nitric oxide (NO) is identified as the primary mediator of endothelial-dependent vasodilation.
- Endothelial function has become a major focus in cardiovascular research.
- Oxidative stress is increasingly recognized as a critical factor in the development of tolerance to organic nitrates.
Purpose of the Study:
- To review the evidence linking oxidative stress to nitrate tolerance.
- To explore how mechanisms of nitrate tolerance may connect with broader concepts of nitric oxide resistance.
Main Methods:
- Literature review of studies on endothelial function, oxidative stress, and nitrate tolerance.
- Synthesis of current theories regarding the role of oxidative stress in drug tolerance.
- Analysis of potential connections between nitrate tolerance and primary nitric oxide resistance.
Main Results:
- Growing evidence supports the theory that oxidative stress contributes to nitrate tolerance.
- Mechanisms of nitrate tolerance appear to be interconnected with fundamental aspects of nitric oxide signaling and resistance.
Conclusions:
- Oxidative stress is a significant factor in the development of tolerance to organic nitrates.
- Understanding these mechanisms provides insight into primary nitric oxide resistance, with implications for cardiovascular health.