Nitric oxide inhibition aggravates ischemic damage of hippocampal but not of nadph neurons in gerbils

Abstract

Background and PurposeNitric oxide may influence patho-physiology of brain ischemia in a complex way depending on the sources of its production either from neurons or endothe-lial cells. We investigated whether inhibition of nitric oxide synthesis affects postischemic neuronal death in hippocampus. Moreover, we evaluated whether the presence of nitric oxide synthase activity in specific neurons protects these against ischemia in the hippocampus, striatum, and sensorimotor cortex. MethodsTo inhibit nitric oxide synthase, several dosing regimens of N°-nitro-L-arginine methyl ester (L-NAME) were used (5 or 50 mg/kg IP, twice a day for 4 days, or 30 mg/kg IV) in gerbils. Control animals received either the isomer NG-nitro-D-arginine methyl ester or the vehicle. The gerbils underwent 10-minute occlusion of carotid arteries under ether anesthesia and controlled body temperature while physiological parameters were monitored. Neuronal damage was assessed 5 days after ischemia using Nissl-stained sections of hippocampus. Nitric oxide synthase neurons were histochem-ically stained for reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity. ResultsL-NAME treatments, but not the chronic one at 5 mg/kg, induced elevation of blood pressure (30% to 80% greater than the control level, P