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Analytical Techniques for Assaying Nitric Oxide Bioactivity
Published on: June 18, 2012
A role for nitric oxide in X-ray contrast material toxicity
E C Lasser1, G E Lamkin, S Lyon
1Department of Radiology, University of California, San Diego, La Jolla 92093-0632, USA.
Nitric oxide (NO) significantly contributes to contrast media toxicity in hyperimmune rats, as shown by 100% lethal dose studies. Inhibiting NO production with L-arginine analogues increased rat tolerance to certain contrast agents.
Area of Science:
- Pharmacology
- Toxicology
- Physiology
Background:
- Contrast media (CM) can cause toxicity, with mechanisms not fully understood.
- Nitric oxide (NO) is implicated in various physiological and pathological processes, including anaphylaxis.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) in contrast media (CM) toxicity.
- To assess the protective effects of modulating NO production on CM-induced lethality in rats.
Main Methods:
- 100% lethal dose (LD100) studies were conducted in hyperimmune Brown Norway (BN) rats and Sprague-Dawley (SD) rats.
- Rats received tail vein injections of contrast media (methylglucamine iothalamate or sodium iothalamate) or methylglucamine hydrochloride.
- Injections were co-administered with L-arginine analogues (to inhibit NO), D-arginine analogues (control), or an H1 blocker.
Main Results:
- L-arginine analogues significantly increased tolerance to methylglucamine iothalamate in BN rats, but not SD rats.
- H1 blockade also enhanced BN rat tolerance to methylglucamine iothalamate and methylglucamine chloride.
- SD rats exhibited better tolerance to CM than BN rats, irrespective of treatment, suggesting strain-specific susceptibility.
Conclusions:
- Nitric oxide (NO) plays a significant role in the LD100 toxicity of contrast media in BN rats.
- Methylglucamine-induced histamine release from mast cells may underlie NO production in this model.
- These findings suggest potential therapeutic targets for mitigating contrast media-induced adverse reactions.
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