Arginine vasopressin stimulation of cerebral microvascular endothelial cell Na-K-Cl cotransporter activity is V1 receptor and [Ca] dependent

Martha E O'Donnell, Vicki Duong, Jimmy Suvatne, Shahin Foroutan, Denise M. Johnson

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Ischemia-induced brain edema formation is mediated by increased transport of Na and Cl across an intact blood-brain barrier (BBB). Our previous studies have provided evidence that a luminally located BBB Na-K-Cl cotransporter is stimulated during cerebral ischemia to increase transport of Na and Cl into the brain. The main focus of the present study was to evaluate the effects of arginine vasopressin (AVP), previously shown to be increased in the brain during ischemia and to promote edema formation, on activity of the BBB cotransporter. Cerebral microvascular endothelial cell (CMEC) monolayers were cultured in astroglial cell conditioned medium, and Na-K-Cl cotransporter activity was assessed as bumetanide-sensitive 86Rb influx. In both human and bovine CMECs, as well as in freshly isolated microvessels, AVP stimulated cotransport activity. This stimulatory effect was mimicked by V1 but not V2 vasopressin agonists and was blocked by V1 but not V2 vasopressin antagonists. Consistent with a V1 vasopressin receptor mechanism of action, AVP caused an increase in CMEC intracellular [Ca] that was blocked by a V1 antagonist. Exposing the cells to [Ca]-free media and/or reducing intracellular [Ca] by BAPTA also blocked AVP stimulation of CMEC cotransporter activity, as did the phospholipase C inhibitor U-73122. Finally, we found that while stimulation of CMEC cotransporter activity by AVP occurred within minutes, it was also sustained for hours in the continued presence of AVP. These findings support the hypothesis that AVP, through a V1 receptor- and [Ca]-dependent mechanism, stimulates the BBB Na-K-Cl cotransporter to participate in ischemia-induced edema formation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Issue number2 58-2
StatePublished - Aug 2005


  • Blood-brain barrier
  • Brain edema
  • Cerebral ischemia
  • Stroke

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology


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