EFFECT OF L-ARGININE AND N-G-NITRO-L-ARGININE ON DELAYED NEURONAL DEATH IN THE GERBIL HIPPOCAMPUS

To assess the role of nitric oxide (NO) in cerebral ischemia, we inves tigated the effect of L-arginine, a substrate of NO synthase (NOS) and N-G-nitro-L-arginine (L-NNA), a NOS inhibitor, on neuronal death in t he CA1 hippocampal region. Seventy-two Mongolian gerbils were used in the study. Both carotid arteries were occluded for 4 min to induce for ebrain ischemia. Temporal muscle temperature was strictly maintained a t 37.5+/-0.3 degrees C during the ischemia. L-arginine (10 and 100 mg kg(-1) I or L-NNA (1, 10 and 100 mg kg(-1) was administered intraperit oneally 4 times: 30 min before, 3h, 6h and 24h after induction of isch emia. Four days after ischemic insult, the animals were perfusion-fixe d, and the neuronal densities in the medial, middle and lateral CA1 su bfield were estimated Average neuronal cell density of the control gro up was 2-3 mm in each subfield. L-arginine at doses of 10 and 100 mg k g(-1) did not prevent neuronal death. L-NNA at doses of 1 and 10 mg kg did not protect neuronal cells from ischemia either. However, in isch emia gerbils treated with 100 mg kg(-1) L-NNA, the average neuronal ce ll density in the lateral CA I subfield was 54.4+/-19.1. L-NNA (100 mg kg(-1)) significantly (p<0.05) reduced the occurrence of neuronal dea th in the lateral CA1 subfield. The present results suggest that NO pl ays an important role in the development of neuronal injury after glob al ischemia.