Release and hemodynamic influence of nitro-glycerine-derived nitric oxide in endotoxemic rats

Abstract

Background and aim Nitric oxide released from nitro-glycerine (NG) has been considered to improve the microcirculation. Septic conditions are, however, associated with excessive formation of nitric oxide (NO), which is formed from l-arginine by the inducible NO synthase (iNOS) activity. Since the characteristics and influence of NG-derived NO in sepsis remains unclear, the major aims of the present study were to quantify the release and to determine the effects of NO formed from NG on systemic blood pressure under endotoxemic conditions. Material and methods Four hours following endotoxin challenge (10 mg/kg intraperitoneally), rats received an infusion of NG (0.5 or 5.0 μmol/kg/h) over 45 min. We determined the changes in blood pressure and the NO concentrations generated in brain, heart, intestine, kidney, liver, and lung by means of NO trapping and EPR technique. Results NG infusion in control rats and endotoxin challenge decreased systemic blood pressure to the same extent. However, in rats subjected to endotoxin challenge NG infusion did not affect the blood pressure. The endotoxin-induced increase in tissue NO concentrations were found to be 15-folds higher than tissue levels of NO following NG infusion. Conclusion Our results suggest that under endotoxic shock conditions in rats NG may not additionally affect the systemic blood pressure. This may relate to the excessive tissue NO levels induced by endotoxin that are not further increased by NG.