Electron Spin Resonance and Chemiluminescence Analyses to Elucidate the Vasodilating Mechanism of Sodium Nitroprusside
| Autor: | Marina Carini, Marica Orioli, Silvia Mazzola, Giancarlo Aldini, Mariangela Albertini, M.G. Clement, Angela Piccoli, Federica Pirrone |
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| Rok vydání: | 2006 |
| Předmět: |
Nitroprusside
Time Factors Endothelium Swine Stereochemistry Vasodilation Nitric Oxide Methemoglobin Nitric oxide law.invention Hemoglobins chemistry.chemical_compound law medicine Animals Electron paramagnetic resonance Chemiluminescence Pharmacology chemistry.chemical_classification Electron Spin Resonance Spectroscopy Transferrin Endothelial Cells Reproducibility of Results medicine.anatomical_structure chemistry Luminescent Measurements Molecular Medicine Sodium nitroprusside medicine.drug |
| Zdroj: | Molecular Pharmacology. 70:1672-1680 |
| ISSN: | 1521-0111 0026-895X |
| Popis: | The aim of this study was to elucidate the vasodilating mechanism of sodium nitroprusside (SNP). To do this, SNP was intravenously infused in pigs (1.67 micromol/kg), and the following paramagnetic metabolites were identified by electron spin resonance: 1) nitrosylhemoglobin [HbFe(II)NO] as an index of the bioconservative pathway; 2) transferrin; 3) [Fe((II))(CN)(5) NO](3-) and [Fe((II))(CN)(4) NO](2-), the reduced penta- and tetracoordinated intermediates of SNP, respectively; and 4) methemoglobin (met-Hb). The results indicate the following: 1) approximately 17% of the dose is converted to HbFe(II)NO at the end of infusion; 2) NO administered as SNP does not undergo bioinactivation (oxidative metabolism), because no significant increase of met-Hb was observed; 3) the equilibrium involving the paramagnetic species of SNP is shifted toward HbFe(II)NO, because a significant increase of transferrin but no detection of the reduced paramagnetic intermediates of SNP was observed. The results obtained indicate that the hemodynamic effect induced by SNP is not mediated by HbFe(II)NO, at least under physiological conditions; hence, a direct release of NO from SNP in the vascular target should be considered. To demonstrate this mechanism, endothelial cells were incubated with SNP, and the release of NO was determined by a novel chemiluminescence method. The results indicate that the endothelium is able to metabolize SNP, with the formation of stoichiometric amounts of NO. In conclusion, SNP is rapidly metabolized to HbFe(II)NO, but the pharmacological response is mediated by a direct mechanism of NO release of the parent compound at the cellular target. |
| Databáze: | OpenAIRE |
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