Dose-Dependent Effects of Nitric Oxide on in Vivo and in Vitro Neuronal Functions

The role of nitric oxide (NO) in mediating ischemia-induced processes is being extensively investigated. Nonetheless, there is still a considerable dispute about the question whether or not NO is cytoprotective or cytotoxic (Choi, 1993), substantiated by a great deal of evidence. On one hand, a vast amount of data attribute a distinct toxic role to NO following ischemia, both in vitro (Dawson et al., 1991), as well as in vivo (Nowicki et al., 1991; Buisson et al., 1992). On the other hand, equally large body of evidence suggest just the opposite both in vivo and in vitro (Sancesario et al., 1994; Pauwels and Lysen, 1992; Demerele-Pallardy et al., 1991). In accord with these recent publications, we observed (Weissman et al., 1992) an enhancement of neuronal death following a 5 min forebrain ischemia in gerbils pretreated with a single high-dose (50 mg/kg, i.p.) of the specific NO synthase (NOS) inhibitor, N G-nitro-L-arginine (NARG). A wide variety of NOS inhibitors was used in the different studies, as well as miscellaneous animal species and various models of brain ischemia (e.g.: focal vs forebrain ischemia; permanent vs transient cessation of blood supply). However, there is very little information on the dose-dependent effect of gradual NOS inhibition on neurophysiological parameters like behavior and histologic-morphometric changes.