Role of N-Nitro-L-Arginine-Methylester in Neuroprotection of Cerebral Ischemic Preconditioning in Rats

Abstract

Background and Aim: Ischemic preconditioning (IPC) is a phenomenon in which brief episodes of ischemia
protect the brain from subsequent, severe ischemic insult. This study evaluated whether the neuroprotective effect of
cerebral IPC is mediated by nitric oxide synthase (NOS) inhibition, using non-selective NOS inhibitor, and N-Nitro-
L-Arginine-Methylester (L-NAME). Materials and Methods: Fifty adult male Wistar rats divided into five groups
ten in each: (1) Sham-operated group (control), (2) ischemia-reperfusion (I/R) group; rats subjected to 30 min of
left common carotid artery (CCA) occlusion followed by 24-h of reperfusion, (3) I/R with NOS inhibition group;
rats infused with L-NAME intraperitoneally 15 min before the same I/R period, (4) IPC group; rats treated with
three 5-min episodes of CCA occlusion (CCAO) with 10 min of reperfusion between stimuli, then 30 min of CCAO
followed by 24 h reperfusion, and (5) IPC with NOS inhibition group: Rats were subjected to the same preconditioning
stimuli as Group 4 with the infusion of NOS inhibitor (L-NAME) 15 mg/kg, 15 min before CCAO. Neurological
assessments were evaluated, enzyme-linked immunosorbent assay used to detect Rho-kinases (ROCK), and nitric
oxide metabolites were measured colorimetrically. Results: IPC significantly reduces the neurological deficit
and lowering the ROCK level with higher nitrite levels. While administration of L-NAME in IPC rats results in a
significant enhancement in neurological scoring compared to IPC without NOS inhibition, with significant inhibition
of nitrite and ROCK. Conclusion: Despite previous evidence that NO involves in neuroprotective mechanism of
IPC, the current data suggest the potential ofL-NAME as a neuroprotective component of IPC.