Central administration of a nitric oxide synthase inhibitor impairs spatial memory in spontaneous hypertensive rats

Nitric oxide is widely recognized as a putative retrograde messenger in the brain. We infused NG-monomethyl-L-arginine (L-NMMA; 25 mg/kg), an inhibitor of nitric oxide synthase (NOS), continuously for a week into the dorsal third ventricle (D3V) of spontaneous hypertensive rate (SHR) by an osmotic infusion pump. Rats administered with L-NMMA showed impaired performance of a radial arm maze task compared with control rats administered with saline. We observed significant reductions of the NOx level in the cerebrospinal fluid (CSF) of the rats administered with L-NMMA, but not in the control rats. Both groups showed no change in systolic blood pressure or serum NOx level. The results provide evidence of a more specific effect of NOS inhibition to the brain independent of alterations in the systemic hemodynamics.