Caracterização das reações do nitroprussiato de sodio com tiois e oxihemoglobina

AUTOR(ES)
DATA DE PUBLICAÇÃO

2003

RESUMO

Nitric oxide (NO) is a messenger molecule synthesized by mammals and plays a large number of biological roles, including the control of arterial pressure, neurotransmission and the inhibition of platelet aggregation. Sodium nitroprusside ([Na2[Fe (CN)5(NO)], SNP) is an NO donor metal complex used clinically for over 70 years in the control of hypertension crisis. Although the use of SNP is widely diffused, its vasodilation mechanism is not fully understood, the first step of it, being considered to be the reduction of the central ion. The main aim of this work was to characterize the reduction reactions of SNP by peptides containing the thiol group (-SH) found endogenously and with oxyhemoglobin (HbO2), in order to obtain kinetics and spectroscopic data which can contribute to the elucidation of its mechanism of action. Through the analysis of spectral changes with time in the IR and UV/VIS ranges, it was found that SNP reacts with L-cysteine (CySH), N-acetyl-L-cysteine (NAC) and glutathione (GSH) in aqueous solution at pH 7,4. Reactions at pH 10 allowed the detection of an intermediate adduct ([Fe(CN)5N(O)SR]), with absorption bands at 521 nm and 2073 cm. The spectroscopic characterization of the reactions have show that the main products resulting from the decomposition of the intermediate are [Fe(CN)5(NO)] and [Fe(CN)5(H2O)] species, the formation of the last implying in the release of NO, as free NO or as the corresponding nitrosothiol (RSNO). In addition the kinetic monitoring of the reactions showed that the rate of decomposition of the intermediate adduct depends on the nature of the peptide and follows the order: CySH >NAC >GSH. SNP was also found to react with HbO2 oxidating it to methemoglobin and nitrate. In the presence of free thiols, the rate of the reaction was found to be increased, indicating a high reactivity of SNP toward HbO2. In vivo tests in an animal model, were SNP and thiols were administered simultaneously have shown a potentiating effect in the three cases. These evidences indicate that the main candidates for the in vivo reduction of SNP whit NO transfer in mammals, are free thiols present in the plasma or in the membrane of endothelial cells.

ASSUNTO(S)

tiois oxido nitrico

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