| Hypertension from Chronic Central Sodium in Mice is Mediated by the Ouabain-Binding Site on the Na, K-ATPase {alpha}2 Isoform. | |
| | |
MedLine Citation:
|
PMID: 21856907 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
A chronic increase in the concentration of sodium in the CSF (↑ CSF [Na]) may be critically important for the development of salt-dependent hypertension. In agreement with this concept, increasing CSF [Na] chronically by intracerebroventricular (i.c.v.) infusion of Na-rich artificial CSF (aCSF-HiNa) in rats produces hypertension by the same brain sytems as that produced by dietary sodium in salt-sensitive strains. We first demonstrate here that i.c.v. aCSF-HiNa for 10 days also causes hypertension in wild-type (WT) mice. We then use both WT and gene-targeted mice to explore the mechanisms. In WT mice with a ouabain-sensitive α2 Na, K-ATPase (α2(S/S)), mean arterial pressure (MAP) rose by ~25 mm Hg within 3 days of starting aCSF-HiNa and remained elevated throughout the study. Ouabain given i.c.v. increased blood pressure to a similar extent. aCSF-HiNa or ouabain given at the same rates s.c. instead of i.c.v. had no effect on blood pressure. The pressor response to i.c.v. aCSF-HiNa was abolished by an anti-ouabain antibody given i.c.v. but not s.c., indicating that it is mediated by an endogenous ouabain-like substance (OLS) in the brain. We compared the effects of i.c.v. aCSF-HiNa or i.c.v. ouabain on blood pressure in α2(S/S) vs. knockout/knockin mice with a ouabain-resistant endogenous α2 subunit (α2(R/R)).In α2(R/R), there was no pressor response to i.c.v. aCSF-HiNa. The α2(R/R) genotype also lacked a pressor response to i.c.v. ouabain. These data demonstrate that chronically ↑ CSF [Na] causes hypertension in mice and that the blood pressure response is mediated by the OLS in the brain, specifically by its binding to the α2 isoform of the Na, K-ATPase. |
| | |
Authors:
|
James W Van Huysse; Iva Dostanic; Jerry B Lingrel; Xiaohong Hou; Hengwei Wu |
Related Documents
:
|
8082847 - A model for fluid mechanisms in sclerostomy. 16322727 - Energy equivalent pressure and total hemodynamic energy associated with the pressure-fl... 15497377 - Physiologic control of rotary blood pumps: an in vitro study. 9535997 - Pst2238: a new antihypertensive compound that antagonizes the long-term pressor effect ... 21247927 - Novel procedure- and device-based strategies in the management of systemic hypertension. 14636297 - Aortic stiffness and carotid intima-media thickness: two independent markers of subclin... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-8-19 |
Journal Detail:
|
Title: American journal of physiology. Heart and circulatory physiology Volume: - ISSN: 1522-1539 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
|
Created Date: 2011-8-22 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
1University of Ottawa Heart Institute. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of h...
Next Document: Cx37 deletion enhances vascular growth and facilitates ischemic limb recovery.