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

Nitric oxide (NO) production in the regenerating liver was estimated from the intensity of the electron paramagnetic resonance (e.p.r.) signal of the mononitrosyl complexes of iron and diethylthiocarbamate (DETC). Preformed complexes of intracellular non-heme Fe2+ and added DETC served as a trap for endogenously produced NO. The time-dependent changes of NO production were connected with the periodicity of liver regeneration. The first increase in NO production occurred ca. 1 h after partial hepatectomy (PHE). The second and more pronounced peak of NO production was observed about 6 h after PHE, when the hepatocytes entered the first cell cycle; it originated mainly from these cells. The following 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 transit from the first to the second cell cycle of the hepatocytes and the entrance of the nonparenchymal cells into proliferation. (C) 1994 Academic Press, Inc.