Modulation of hemorrhagic shock by intestinal mucosal NG-nitro-L-arginine and L-arginine in the anesthetized rat.

Maintaining intestinal function protects against shock of various origins. Nitric oxide (NO) can protect tissues. The present research examined whether the presence of 50 microM NG-nitro-L-arginine (NOLARG), a nitric oxide synthase (NOS) inhibitor, or L-arginine (LARG), the substrate of NOS, in the jejunal lumen of the anesthetized rat could affect the progress of hemorrhagic shock. The jejunal lumen was perfused with saline containing 14C-inulin and 3H2O to measure net H2O absorption and absorptive site blood flow (ASBF). Luminal NOx (NO3- +NO2-) secretion into the gut effluent and blood pressure (BP) were also measured. The animals were bled to and maintained at 40 mmHg for 60 min and then reinfused. Survival time was significantly decreased in luminally-perfused NOLARG animals, but was significantly increased in LARG perfused animals. Most deaths occurred during the hemorrhage periods. Animals perfused with LARG through the ileal lumen required significantly less blood to be reinfused to maintain blood pressure during the hemorrhage periods. There were not significant differences in BP among surviving animals. Net H2O absorption and ASBF were significantly decreased only in NOLARG-perfused animals in the period just before and after reinfusion. There were no significant differences in luminal NOx secretion among the groups. Thus, intestinal mucosal NOS substrates or antagonists modulate the progress of hemorrhagic shock, but the mechanism was not defined in these experiments.