Response of the Nitric Oxide System to Hypobaric Hypoxia in the Aged Striatum

Abstract

Background: Nitric oxide (NO) appears to play a key role in the hypoxic injury to the brain. We have previously reported that hypoxia/reoxygenation downregulated NO synthases (NOS) in the adult striatum. Until now, no data were available concerning the influence of aging in conjunction with hypoxia/reoxygenation on the NO system in the striatum. Objective: The aim of this study was to assess the role of the NO pathway in the hypoxic aged striatum. Methods: Wistar rats 24-25 months old were submitted to hypobaric hypoxia (20 min)/reoxygenation (0 h, 24 h, 5 days). Expression (PCR, immunohistochemistry/image analysis) and activity (NADPH-diaphorase/image analysis) of NOS isoforms (neuronal NOS or nNOS, endothelial NOS or eNOS, inducible NOS or iNOS) were analyzed together with nitrated protein expression (immunohistochemistry/image analysis). NO levels were indirectly quantified as nitrates/nitrites (NOx). Results: The mRNA levels of NOS isoforms were undetectable at 0 h after hypoxia in the striatum compared to the control. At later reoxygenation times, nNOS mRNA decreased, while eNOS mRNA augmented. Protein levels of nNOS and eNOS rose at 24 h after hypoxia, and iNOS protein increased at 5 days. NOx levels remained unchanged, whereas in situ NOS activity and protein nitration diminished during reoxygenation in the aged striatum. Conclusion: The aged striatum may overexpress NOS isoforms as a neuroprotective-adaptive mechanism to hypoxia. However, this mechanism may not work properly in the aged striatum, since no changes in NO levels were detected after hypoxia. This may be related to the low activity of NOS isoforms in the hypoxic striatum.