EPR EVIDENCE OF NITRIC-OXIDE PRODUCTION BY THE REGENERATING RAT-LIVER

Nitric oxide (NO) production in the regenerating liver was estimated f rom the intensity of the electron paramagnetic resonance (e.p.r.) sign al of the mononitrosyl complexes of iron and diethylthiocarbamate (DET C). Preformed complexes of intracellular non-heme Fe2+ and added DETC served as a trap for endogenously produced NO. The time-dependent chan ges of NO production were connected with the periodicity of liver rege neration. The first increase in NO production occurred ca. 1 h after p artial hepatectomy (PHE). The second and more pronounced peak of NO pr oduction was observed about 6 h after PHE, when the hepatocytes entere d the first cell cycle; it originated mainly from these cells. The fol lowing minimum of NO synthesis coincided with the maximal rate of DNA synthesis. The third gradual rise of NO production was seen at the end of the investigated period that covered the G(2)+M phases, the transi t from the first to the second cell cycle of the hepatocytes and the e ntrance of the nonparenchymal cells into proliferation. (C) 1994 Acade mic Press, Inc.