A study for a role of inducible NO synthase in septic rats with cecal ligation and puncture (CLP)

Since inducible NO synthase (iNOS; type II) is suggested to be critical for multiple organ failure in septic syndrome because of its profound production of NO, we studied a role of iNOS in septic lung injury produced by CLP in rats. Effects of a nobel selective iNOS inhibitor(ONO-1714) were studied in the CLP-rats. More than 90% of CLP-rats died within 48 h after this intervention and pulmonary histological findings showed edematous change and cellular infiltration in interstitium. Injection of ONO-1714 at 0.03 mg/kg every 12h resulted in significantly higher survival rates than the saline control if the administration was started at 12h after the CLP. The other administration schedule which started immediately or at 6h after the intervention did not show any improvement in survival rates compared with the saline. NOx levels in plasma significantly increased at 12 h after the intervention and thereafter further increased in parallel with the time elapsed. However, iNOS protein expression in lung homogenates showed maximum level at around 18-24 h after the intervention. The rats started to be treated with ONO-1714 at 12h after the operation showed significantly reduced NOx levels in plasma in comparison with the saline control, but did not alter time-course of iNOS expression in lung homogenates. In conclusion treatment with a selective iNOS inhibitor improves survival of the CLP-rats.