On the nature of a compound formed from dinitrosyl-iron complexes with cysteine and responsible for a long-lasting vasorelaxation

Abstract

The nature of a compound able to induce long-lasting (⩾20 min) relaxation of rat abdominal aorta rings after addition of rapidly (within several minutes) disappeared mono- and binuclear dinitrosyl iron complexes with cysteine (M- and B-DNICs, respectively) (10 μmol) to the Krebs medium has been investigated. It has been found that long-lasting vasorelaxation is not induced either by S-nitrosocysteine formed upon decomposition of DNICs or by accumulation of free nitric oxide molecules or nitrite remaining in the incubation medium. Long-term air bubbling of the Krebs medium initially containing М-DNIC is accompanied by conversion of the complex first into B-DNIC, which represents a Roussin’s red salt cysteine ester and then into a more stable diamagnetic compound Х, which displays an intense absorption band at 278 nm. Compound X is decomposed after treatment with the strong bivalent iron chelator bathophenanthroline disulfonate (BPDS) and N-methyl- d-glucamine dithiocarbamate (MGD). The MGD-induced decomposition of compound Х is concomitant with the formation of EPR-detectable mononitrosyl iron complexes with MGD. Treatment of compound X with cysteine results in its decomposition and the appearance of optical absorption bands characteristic of М- and B-DNICs. Evidently, compound Х, has an iron-nitrosyl origin similar to that of М- and B-DNICs and its formation in oxygenated DNIC solutions is determined by the lowering cysteine content in them. It is hypothesized that compound X represents a cysteine ester of nitrosyl iron complexes, namely, a black Roussin’s salt cysteine ester responsible for long-lasting vasorelaxation initiated by addition of М- and B-DNICs that are rapidly decomposed to compound X to the incubation medium.