{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:57:20Z","timestamp":1793451440072,"version":"4.5.0"},"reference-count":24,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,4,2]]},"abstract":"<jats:p>\n                    To uncover the potential cardiovascular effects of human polymorphisms influencing transforming growth factor \u03b21 (TGF\u03b21) expression, we generated mice with\n                    <jats:italic>Tgfb1<\/jats:italic>\n                    mRNA expression graded in five steps from 10% to 300% normal. Adrenal expression of the genes for mineralocorticoid-producing enzymes ranged from 50% normal in the hypermorphs at age 12 wk to 400% normal in the hypomorphs accompanied with proportionate changes in plasma aldosterone levels, whereas plasma volumes ranged from 50% to 150% normal accompanied by marked compensatory changes in plasma angiotensin II and renin levels. The aldosterone\/renin ratio ranged from 0.3 times normal in the 300% hypermorphs to six times in the 10% hypomorphs, which have elevated blood pressure. Urinary output of water and electrolytes are markedly decreased in the 10% hypomorphs without significant change in the glomerular filtration rate. Renal activities for the Na\n                    <jats:sup>+<\/jats:sup>\n                    , K\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase, and epithelial sodium channel are markedly increased in the 10% hypomorphs. The hypertension in the 10% hypomorphs is corrected by spironolactone or amiloride at doses that do not change blood pressure in wild-type mice. Thus, changes in\n                    <jats:italic>Tgfb1<\/jats:italic>\n                    expression cause marked progressive changes in multiple systems that regulate blood pressure and fluid homeostasis, with the major effects being mediated by changes in adrenocortical function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1302641110","type":"journal-article","created":{"date-parts":[[2013,3,16]],"date-time":"2013-03-16T04:29:51Z","timestamp":1363408191000},"page":"5600-5605","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":30,"title":["Primary aldosteronism and impaired natriuresis in mice underexpressing TGF\u03b21"],"prefix":"10.1073","volume":"110","author":[{"given":"Masao","family":"Kakoki","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleh M.","family":"Pochynyuk","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Hathaway","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Tomita","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Hagaman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 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