On the nature of a compound formed from dinitrosyl-iron complexes with cysteine and responsible for a long-lasting vasorelaxation.
The nature of a compound able to induce long-lasting (> or =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 micromol) 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 M-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 X, 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 X 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 M- and B-DNICs. Evidently, compound X, has an iron-nitrosyl origin similar to that of M- 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 M- and B-DNICs that are rapidly decomposed to compound X to the incubation medium.
Mokh
Vladimir P
VP
Russian Cardiology Research-and-Production Complex, Moscow, Russia.
Poltorakov
Alexander P
AP
Serezhenkov
Vladimir A
VA
Vanin
Anatoly F
AF
D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D007501:Iron / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D009589:Nitrogen Oxides / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026403:S-Nitrosothiols / Q000737:chemistry* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000737:chemistry* / Q000494:pharmacology
D009589:Nitrogen Oxides; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; C073661:dinitrosyl iron complex; C021315:S-nitrosocysteine; D007501:Iron; D003545:Cysteine