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Cerebral microvascular nNOS responds to lowered oxygen tension through a bumetanide- sensitive cotransporter and sodium-calcium exchanger.
- Source :
-
American Journal of Physiology: Heart & Circulatory Physiology . May2008, Vol. 294 Issue 5, pH2166-H2173. 8p. 9 Graphs. - Publication Year :
- 2008
-
Abstract
- Na+ cotransporters have a substantial role in neuronal damage during brain hypoxia. We proposed these cotransporters have beneficial roles in oxygen-sensing mechanisms that increase periarteriolar nitric oxide (NO) concentration ([NO]) during mild to moderate oxygen deprivation. Our prior studies have shown that cerebral neuronal NO synthase (nNOS) is essential for [NO] responses to decreased oxygen tension and that endothelial NO synthase (eNOS) is of little consequence. In this study, we explored the mechanisms of three specific cotransporters known to play a role in the hypoxic state: KB-R7943 for blockade of the Na+/Ca2+ exchanger, bumetanide for the Na+-K+-2Cl cotransporter, and amiloride for Na+/H+ cotransporters. In vivo measurements of arteriolar diameter and [NO] at normal and locally reduced oxygen tension in the rat parietal cortex provided the functional analysis. As previously found for intestinal arterioles, bumetanide- sensitive cotransporters are primarily responsible for sensing reduced oxygen because the increased [NO] and dilation were suppressed. The Na+/Ca2+ exchanger facilitated increased NO formation because blockade also suppressed [NO] and dilatory responses to decreased oxygen. Amiloride-sensitive Na+/H+ cotransporters did not significantly contribute to the microvascular regulation. To confirm that nNOS rather than eNOS was primarily responsible for NO generation, eNOS was suppressed with the fusion protein cavtratin for the caveolae domain of eNOS. Although the resting [NO] decreased and arterioles constricted as eNOS was suppressed, most of the increased NO and dilatory response to oxygen were preserved because nNOS was functional. Therefore, nNOS activation secondary to Na+-K+- 2Cl- cotransporter and Na+/Ca2+ exchanger functions are key to cerebral vascular oxygen responses. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03636135
- Volume :
- 294
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Heart & Circulatory Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 32079259
- Full Text :
- https://doi.org/10.1152/ajpheart.01074.2007