Oxidative release of nitric oxide accounts for guanylyl cyclase stimulating, vasodilator and anti-platelet activity of Piloty's acid: a comparison with Angeli's salt
Zamora, R., Grzesiok, A., Weber, H. and Feelisch, M. (1995) Oxidative release of nitric oxide accounts for guanylyl cyclase stimulating, vasodilator and anti-platelet activity of Piloty's acid: a comparison with Angeli's salt. The Biochemical Journal, 312 (Pt 2), 333-339. (PMID:8526840).
The decomposition of benzenesulphohydroxamic acid (Piloty's acid; PA) and some of its derivatives has been reported to yield nitroxyl ions (NO-), a species with potent vasodilator properties. In a previous study we demonstrated that the oxidative breakdown of PA results in the formation of nitric oxide (NO) and suggested that NO rather than NO- may account for its vasorelaxant properties. Using isolated aortic rings in organ baths, we now show that high concentrations of cysteine potentiate the vasorelaxant response to PA, whereas responses to Angeli's salt (AS), a known generator of NO-, were almost completely inhibited. These different behaviours of PA and AS are mirrored by their distinct chemistries. By using HPLC it was shown that, at physiological pH and in the absence of oxidizing conditions, PA is a relatively stable compound. Direct chemical determination of NO, stimulation of soluble guanylyl cyclase, and measurement of platelet aggregation under various experimental conditions confirmed the requirement for oxidation to release NO from PA, and quite weak oxidants were found to be sufficient to promote this reaction. In contrast, at pH 7.4 AS decomposed rapidly to yield nitrite (NO2-) and NO-, bu did not produce NO on reaction with dioxygen (O2) or hydrogen peroxide (H2O2). Thus sulphohydroxamic acids are a new class of thiol-independent NO-donors that generate NO rather than NO- under physiological conditions.
|Subjects:||Q Science > QP Physiology
Q Science > QR Microbiology > QR180 Immunology
|Divisions :||Faculty of Medicine > Clinical and Experimental Sciences
|Accepted Date and Publication Date:||
|Date Deposited:||29 Jun 2012 14:30|
|Last Modified:||31 Mar 2016 14:27|
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