{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:23:01Z","timestamp":1787016181436,"version":"build-2736575974"},"reference-count":188,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ouabain\u2010induced hypertension is a multifactorial and condition\u2010dependent phenomenon involving coordinated actions across vascular, renal and central nervous system pathways. At the vascular level, ouabain inhibits Na\u207a\/K\u207a\u2010ATPase, particularly the \u03b12\u2010isoform, leading to elevated intracellular Ca\n                    <jats:sup>2<\/jats:sup>\n                    \u207a, enhanced vasoconstriction and structural remodelling of resistance arteries. These effects are exacerbated by oxidative stress, inflammation, and altered expression of Ca\n                    <jats:sup>2<\/jats:sup>\n                    \u207a\u2010mobilizing proteins such as NCX1 and TRPC channels. In the kidney, ouabain disrupts Na\n                    <jats:sup>+<\/jats:sup>\n                    handling, especially in the proximal tubule, suppresses natriuretic pathways like the D1 dopamine receptor, and promotes volume expansion through renal and sympathetic mechanisms. Centrally, ouabain acts on sodium\u2010sensitive brain regions, including the median preoptic nucleus, rostral ventrolateral medulla and paraventricular nucleus, where it increases sympathetic outflow and impairs baroreflex control. These effects are potentiated by local interactions with brain\u2010derived angiotensin II and cerebrospinal Na\u207a, independent of peripheral ouabain levels. However, the hypertensive response is not universal and may vary by strain, salt status, genetic background and experimental conditions. These insights carry important translational implications. Elevated levels of endogenous ouabain (EO) have been identified in patients with salt\u2010sensitive, low\u2010renin or neurogenic hypertension. Therapeutic strategies targeting ouabain\u2010sensitive pathways include isoform\u2010selective Na\u207a\/K\u207a\u2010ATPase modulators, NCX or TRPC inhibitors, and agents acting on the central renin\u2013angiotensin system. EO\u2010neutralizing therapies such as digoxin antibodies may also hold clinical promise. Personalized medicine approaches incorporating EO sensitivity markers and genotype\u2010specific models may advance the management of resistant hypertension and deepen our understanding of ouabain's dual role as both physiological modulator and pathological trigger.\n                  <\/jats:p>","DOI":"10.1113\/ep092956","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T10:53:47Z","timestamp":1754477627000},"page":"653-673","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ouabain\u2010induced hypertension in rats: Mechanisms, variability and translational implications"],"prefix":"10.1113","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7931-156X","authenticated-orcid":false,"given":"Priscilla Rodrigues O.","family":"Feij\u00f3","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia Bioqu\u00edmica e Molecular, Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0767-1240","authenticated-orcid":false,"given":"Luis Eduardo M.","family":"Quintas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia Bioqu\u00edmica e Molecular, Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro  Rio de Janeiro 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