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The Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase \u03b1 (catalytic)-isoform(s) that mediates the pressor response to increased CSF [Na] is unknown, but it is likely that one or more isoforms that bind ouabain with high affinity are involved (e.g., the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase \u03b1<jats:sub>2<\/jats:sub>- and\/or \u03b1<jats:sub>3<\/jats:sub>-subunits). We hypothesize that OLS-induced inhibition of the \u03b1<jats:sub>2<\/jats:sub>-subunit mediates this response. Therefore, a chronic reduction in \u03b1<jats:sub>2<\/jats:sub>expression via a heterozygous gene knockout (\u03b1<jats:sub>2<\/jats:sub>+\/\u2212) should enhance the pressor response to increased CSF [Na]. Intracerebroventricular (ICV) infusion of artificial CSF containing 0.225 M NaCl increased mean arterial pressure (MAP) in both wild-type (+\/+) and \u03b1<jats:sub>2<\/jats:sub>+\/\u2212 mice, but to a greater extent in \u03b1<jats:sub>2<\/jats:sub>+\/\u2212. Likewise, the pressor response to ICV ouabain was enhanced in \u03b1<jats:sub>2<\/jats:sub>+\/\u2212 mice, demonstrating enhanced sensitivity to brain Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase inhibition per se. The pressor response to ICV ANG I but not ANG II was also enhanced in \u03b1<jats:sub>2<\/jats:sub>+\/\u2212 vs. \u03b1<jats:sub>2<\/jats:sub>+\/+ mice, suggesting an enhanced brain RAS activity that may be mediated by increased brain angiotensin converting enzyme (ACE). The latter hypothesis is supported by enhanced ACE ligand binding in the organum vasculosum laminae terminalis. These studies demonstrate that chronic downregulation of Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase \u03b1<jats:sub>2<\/jats:sub>-isoform expression by heterozygous knockout increases the pressor response to increased CSF [Na] and activates the brain RAS. Since these changes mimic those produced by the endogenous brain OLS, the brain \u03b1<jats:sub>2<\/jats:sub>-isoform may be a target for the brain OLS during increases in CSF [Na], such as in salt-dependent hypertension.<\/jats:p>","DOI":"10.1152\/ajpregu.00809.2007","type":"journal-article","created":{"date-parts":[[2009,2,26]],"date-time":"2009-02-26T03:06:26Z","timestamp":1235617586000},"page":"R1427-R1438","source":"Crossref","is-referenced-by-count":20,"title":["Enhanced pressor response to increased CSF sodium concentration and to central ANG I in heterozygous \u03b1<sub>2<\/sub>Na<sup>+<\/sup>-K<sup>+<\/sup>-ATPase knockout mice"],"prefix":"10.1152","volume":"296","author":[{"given":"Xiaohong","family":"Hou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven F.","family":"Theriault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iva","family":"Dostanic-Larson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy E.","family":"Moseley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry B","family":"Lingrel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hengwei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Dean","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W.","family":"Van Huysse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.47.33183"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Bastide F, Meissner G, Fleischer S, Post RL.Similarity of the active site of phosphorylation of the adenosine triphosphatase from transport of sodium and potassium ions in kidney to that for transport of calcium ions in the sarcoplasmic reticulum of muscle.J Biol Chem248: 8385\u20138391, 1973.","DOI":"10.1016\/S0021-9258(19)43145-1"},{"key":"R3","unstructured":"Baxter-Lowe LA, Hokin LE.The Red Cell Membrane: A Model for Solute Transport, edited by Raess BU and Tunnicliff G. 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