Nitric oxide as a regulatory factor for aquaporin-1 and 4 gene expression following brain ischemia/reperfusion injury in rat.

Although the role of aquaporin-4 (AQP4) and aquaporin-1 (AQP1) channels in ischemia-induced brain edema has been previously reported, nitric oxide (NO) modulation of these channels has not been investigated. The aim of this study was to evaluate the NO modulation of AQPs gene expression after brain ischemia/reperfusion (I/R) in rats. The experiment was performed in three groups of rats: sham, control ischemic and L-NAME pretreated (1 mg/kg). Brain ischemia was induced by 60 min middle cerebral artery occlusion (MCAO) under continuous recording of regional cerebral blood flow (rCBF) followed by 12 h reperfusion. Brain edema was assessed by dry/wet method, and Quantitative RT-PCR was used for assessment of mRNA levels of AQPs. There was 80% reduction in rCBF during MCAO. Brain cerebral ischemia elevated the brain water content from 78.66±0.17% to 81.93±0.60%, and inhibition of NO production by L-NAME significantly reduced this elevation (79.74±0.79%). The mRNA expression of AQP1 increased, but AQP4 decreased in response to I/R. l-NAME pretreatment significantly decreased AQP1 mRNA and prevented the reduction of AQP4 mRNA. The findings of this study indicated that brain I/R injury provokes brain edema by alterations of AQPs expression, and the NO is the main signaling factor that modulates gene expression of these channels.