Abstract
Cerebral edema formation in ischemic stroke involves increased activity of blood‐brain barrier (BBB) Na transporters through mechanisms not well understood. Na/H exchange inhibitors can reduce brain edema in rat models of ischemic stroke. We have found previously that cerebral microvascular endothelial cells (CMEC) express both NHE1 and NHE2 isoforms of the Na/H exchanger and that CMEC exchanger activity is stimulated by the ischemic factors hypoxia, aglycemia and arginine vasopressin (AVP). In the present study we evaluated BBB in situ for the presence of NHE isoforms and further, investigated the mechanism by which AVP stimulates the BBB Na/H exchanger. Western blot analysis and immunoelectron microscopy were used to evaluate NHE isoforms in freshly isolated rat cerebral microvessels and perfusion‐fixed rat brain, respectively. In addition, Na/H exchange activity of CMEC was evaluated by microspectrofluorometry, using the pH‐sensitive dye BCECF. NHE1 and NHE2 isoforms were found in the microvessels and in BBB in situ, with both isoforms predominantly in the luminal BBB membrane (70% for NHE1, 75% for NHE2). CMEC Na/H exchange activity was increased 2.3‐fold by AVP and 2.5‐fold by the V1 agonist Orn VP (both 100 nM, 5 min) but not by a V2 agonist (DDAVP). Our findings suggest that AVP stimulates luminal BBB NHE1 and/or NHE2 activity via a V1 AVP receptor pathway.Supported by NINDS and AHA Western States Affiliate
Published Version
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