NITRIC-OXIDE IS RELEASED IN REGENERATING LIVER AFTER PARTIAL-HEPATECTOMY

The induction of hepatic nitric oxide synthase (NOS) and the biosynthe sis of nitric oxide (NO) were studied in Liver after partial hepatecto my (PN). NOS activity in the liver remnant was observed 4 to 6 hours a fter PH, and no differences were evidenced between the proximal and di stal surgical areas. The form of NOS expressed in liver was independen t of calcium and calmodulin, and the messenger RNA levels were first d etected 2 hours after hepatectomy using a probe corresponding to the c ytokine-induced macrophage NOS, The seric concentration of nitrites re mained unchanged after hepatectomy, whereas the content in nitrates an d in S-nitrosylated proteins progressively increased in parallel with the NOS activity, The spectra of hemoglobin in the 400- to 460-nm regi on failed to exhibit the characteristic shift caused by the formation of the nitrosyl-hemoglobin complex, suggesting that NO was rapidly met abolized in liver, Treatment of the animals with substrate analogue NO S inhibitors blocked the pattern of DNA ploidy elicited after hepatect omy, suggesting a role for NO in the regenerative process. Peritoneal resident macrophages were used as an alternative reporter cell system for the assessment of NOS expression. Incubation ex vivo of peritoneal macrophages from animals that underwent hepatectomy induced the expre ssion of NOS in a cytokine-modulated fashion, suggesting that macropha ges were primed as a result of the hepatectomy, When peritoneal macrop hages from control rats were incubated with the sera of animals that u nderwent hepatectomy, a time-dependent induction of NOS was observed, with a maximal induction corresponding to sera collected 2 hours after PB These results indicate that NO might be involved in the control of early responses after PH.