| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology and Membrane Biology, University of California, Davis, CA, USA
* To whom correspondence should be addressed. E-mail: meodonnell{at}ucdavis.edu.
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 CMEC, 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 by 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 U73122. 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 to ischemia-induced edema formation.
This article has been cited by other articles:
|
|
 |
|
  T. I. Lam, P. M. Wise, and M. E. O'Donnell Cerebral microvascular endothelial cell Na/H exchange: evidence for the presence of NHE1 and NHE2 isoforms and regulation by arginine vasopressin Am J Physiol Cell Physiol, August 1, 2009; 297(2): C278 - C289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Brillault, T. I. Lam, J. M. Rutkowsky, S. Foroutan, and M. E. O'Donnell Hypoxia effects on cell volume and ion uptake of cerebral microvascular endothelial cells Am J Physiol Cell Physiol, January 1, 2008; 294(1): C88 - C96. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hom, M. A. Fleegal, R. D. Egleton, C. R. Campos, B. T. Hawkins, and T. P. Davis Comparative changes in the blood-brain barrier and cerebral infarction of SHR and WKY rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1881 - R1892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. F. Pedersen, M. E. O'Donnell, S. E. Anderson, and P. M. Cala Physiology and pathophysiology of Na+/H+ exchange and Na+-K+-2Cl- cotransport in the heart, brain, and blood Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2006; 291(1): R1 - R25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Foroutan, J. Brillault, B. Forbush, and M. E. O'Donnell Moderate-to-severe ischemic conditions increase activity and phosphorylation of the cerebral microvascular endothelial cell Na+-K+-Cl- cotransporter Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1492 - C1501. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
