Primary aldosteronism and impaired natriuresis in mice underexpressing TGFβ1

Masao Kakoki, Oleh M. Pochynyuk, Catherine M. Hathaway, Hirofumi Tomita, John R. Hagaman, Hyung Suk Kim, Oleg L. Zaika, Mykola Mamenko, Yukako Kayashima, Kota Matsuki, Sylvia Hiller, Feng Li, Longquan Xu, Ruriko Grant, Alejandro M. Bertorello, Oliver Smithies

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


To uncover the potential cardiovascular effects of human polymorphisms influencing transforming growth factor β1 (TGFβ1) expression, wegenerated mice with Tgfb1mRNAexpression 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+, K+-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 Tgfb1 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.

Original languageEnglish (US)
Pages (from-to)5600-5605
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number14
StatePublished - Apr 2 2013
Externally publishedYes


  • Hyperthermia
  • Idiopathic bilateral adrenal hyperplasia

ASJC Scopus subject areas

  • General


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