{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T06:53:54Z","timestamp":1759042434343},"reference-count":33,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:p>A chronic increase in the concentration of sodium chloride in the cerebrospinal fluid (CSF) (\u2191CSF [NaCl]) appears to be critically important for the development of salt-dependent hypertension. In agreement with this concept, increasing CSF [NaCl] chronically by intracerebroventricular (icv) infusion of NaCl-rich artificial CSF (aCSF-HiNaCl) in rats produces hypertension by the same mechanisms (i.e., aldosterone-ouabain pathway in the brain) as that produced by dietary sodium in salt-sensitive strains. We first demonstrate here that icv aCSF-HiNaCl for 10 days also causes hypertension in wild-type (WT) mice. We then used both WT and gene-targeted mice to explore the mechanisms. In WT mice with a ouabain-sensitive Na,K-ATPase \u03b1<jats:sub>2<\/jats:sub>-isoform (\u03b12<jats:sup>S\/S<\/jats:sup>), mean arterial pressure rose by \u223c25 mmHg within 2 days of starting aCSF-HiNaCl (0.6 nmol Na\/min) and remained elevated throughout the study. Ouabain (171 pmol\/day icv) increased blood pressure to a similar extent. aCSF-HiNaCl or ouabain given at the same rates subcutaneously instead of intracerebroventricularly had no effect on blood pressure. The pressor response to icv aCSF-HiNaCl was abolished by an anti-ouabain antibody given intracerebroventricularly but not subcutaneously, indicating that it is mediated by an endogenous ouabain-like substance in the brain. We compared the effects of icv aCSF-HiNaCl or icv ouabain on blood pressure in \u03b12<jats:sup>S\/S<\/jats:sup>versus knockout\/knockin mice with a ouabain-resistant endogenous \u03b1<jats:sub>2<\/jats:sub>-subunit (\u03b12<jats:sup>R\/R<\/jats:sup>). In \u03b12<jats:sup>R\/R<\/jats:sup>, there was no pressor response to icv aCSF-HiNaCl in contrast to WT mice. The \u03b12<jats:sup>R\/R<\/jats:sup>genotype also lacked a pressor response to icv ouabain. These data demonstrate that chronic \u2191CSF [NaCl] causes hypertension in mice and that the blood pressure response is mediated by the ouabain-like substance in the brain, specifically by its binding to the \u03b1<jats:sub>2<\/jats:sub>-isoform of the Na,K-ATPase.<\/jats:p>","DOI":"10.1152\/ajpheart.01216.2010","type":"journal-article","created":{"date-parts":[[2011,8,22]],"date-time":"2011-08-22T21:44:32Z","timestamp":1314049472000},"page":"H2147-H2153","source":"Crossref","is-referenced-by-count":23,"title":["Hypertension from chronic central sodium chloride in mice is mediated by the ouabain-binding site on the Na,K-ATPase \u03b1<sub>2<\/sub>-isoform"],"prefix":"10.1152","volume":"301","author":[{"given":"James W.","family":"Van Huysse","sequence":"first","affiliation":[{"name":"Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada;"},{"name":"Departments of Medicine and Biochemistry, Microbiology and Immunology, University of Ottawa, Ontario, Canada; 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