Direct demonstration of nitric oxide formation in organs of rabbits treated by transdermal glyceryl trinitrate using an in vivo spin trapping technique
| Autor: | Olivier Bouchot, Gaëlle Clermont, Véronique Maupoil, Catherine Vergely, Luc Rochette, Sandrine Lecour, Caroline Perrin, Marianne Zeller |
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| Rok vydání: | 2003 |
| Předmět: |
Time Factors
Heart Ventricles Vasodilator Agents Aorta Thoracic Blood Pressure Vena Cava Inferior Pharmacology Administration Cutaneous Kidney Nitric Oxide Inferior vena cava Nitric oxide Hemoglobins Nitroglycerin chemistry.chemical_compound Heart Rate Thiocarbamates In vivo medicine.artery medicine Renal medulla Animals Sorbitol Pharmacology (medical) Ferrous Compounds Nitrites Transdermal Dosage Forms Aorta Nitrates Lagomorpha biology Chemistry biology.organism_classification medicine.anatomical_structure Liver medicine.vein Organ Specificity Anesthesia Injections Intravenous cardiovascular system Spin Labels Rabbits Spin Trapping Spleen circulatory and respiratory physiology |
| Zdroj: | Fundamental & Clinical Pharmacology. 17:709-715 |
| ISSN: | 1472-8206 0767-3981 |
| DOI: | 10.1046/j.1472-8206.2003.00199.x |
| Popis: | Glyceryl trinitrate (GTN) is commonly delivered by a patch for the treatment of angina pectoris. The idea is now generally accepted that GTN requires a biotransformation process that activates the drug, in particular through nitric oxide (NO) generation. However, the pharmacokinetics of NO delivery from GTN still remains obscure. The objective of this study was to assess GTN-derived NO formation in vascular tissues and organs in rabbit given GTN patches. NO levels were evaluated in rabbits after 3 h of treatment with a 10 mg GTN patch (GTN group; n = 7) or a placebo patch (CTL; n = 7). Nitrosylhaemoglobin (HbNO) was evaluated by electron spin resonance (ESR) spectroscopy in red cell suspension. In vivo spin trapping technique using FeMGD as a spin trap, associated with ESR was used to quantify NO in tissues. The NO-spin trap complex, which is a relatively stable product, has been measured in several tissues. The ESR spectrum corresponding to HbNO was not found in red cell of GTN or CTL rabbits. The spectrum corresponding to the NO-spin trap complex was observed in all analysed tissues of CTL rabbits. The signal was significantly increased in liver, renal medulla, heart left ventricle and spleen of GTN-treated rabbits, and to a lesser extent in right ventricle and lung. No difference was shown between NO-spin trap levels measured in aorta or inferior vena cava from GTN or CTL rabbits. These data suggest that GTN patch treatment induced NO release, and that tissue-specific differences in transdermal GTN-derived NO exist. The GTN-NO pathway appears to be largely involved in organs such as the liver, kidney and heart. |
| Databáze: | OpenAIRE |
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