OXIDATIVE RELEASE OF NITRIC-OXIDE ACCOUNTS FOR GUANYLYL CYCLASE STIMULATING, VASODILATOR AND ANTIPLATETLET ACTIVITY OF PILOTYS ACID - A COMPARISON WITH ANGELIS SALT

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 stud y we demonstrated that the oxidative breakdown of PA results in the fo rmation 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 poten tiate the vasorelaxant response to PA, whereas responses to Angeli's s alt (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 com pound. Direct chemical determination of NO, stimulation of soluble gua nylyl cyclase, and measurement of platelet aggregation under various e xperimental conditions confirmed the requirement for oxidation to rele ase 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 t o yield nitrite (NO2-) and NO-, but did not produce NO on reaction wit h dioxygen (O-2) or hydrogen peroxide (H2O2). Thus sulphohydroxamic ac ids are a new class of thiol-independent NO-donors that generate NO ra ther than NO- under physiological conditions.