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 journalArticle

21 Citations (Scopus)

Abstract

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
Volume110
Issue number14
DOIs
StatePublished - Apr 2 2013
Externally publishedYes

Fingerprint

Natriuresis
Hyperaldosteronism
Transforming Growth Factors
Blood Pressure
Aldosterone
Renin
Epithelial Sodium Channels
Mineralocorticoids
Spironolactone
Plasma Volume
Amiloride
Glomerular Filtration Rate
Angiotensin II
Electrolytes
Homeostasis
Hypertension
Kidney
Gene Expression
Water
Enzymes

Keywords

  • Hyperthermia
  • Idiopathic bilateral adrenal hyperplasia

ASJC Scopus subject areas

  • General

Cite this

Kakoki, M., Pochynyuk, O. M., Hathaway, C. M., Tomita, H., Hagaman, J. R., Kim, H. S., ... Smithies, O. (2013). Primary aldosteronism and impaired natriuresis in mice underexpressing TGFβ1. Proceedings of the National Academy of Sciences of the United States of America, 110(14), 5600-5605. https://doi.org/10.1073/pnas.1302641110

Primary aldosteronism and impaired natriuresis in mice underexpressing TGFβ1. / Kakoki, Masao; Pochynyuk, Oleh M.; Hathaway, Catherine M.; Tomita, Hirofumi; Hagaman, John R.; Kim, Hyung Suk; Zaika, Oleg L.; Mamenko, Mykola; Kayashima, Yukako; Matsuki, Kota; Hiller, Sylvia; Li, Feng; Xu, Longquan; Grant, Ruriko; Bertorello, Alejandro M.; Smithies, Oliver.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 14, 02.04.2013, p. 5600-5605.

Research output: Contribution to journalArticle

Kakoki, M, Pochynyuk, OM, Hathaway, CM, Tomita, H, Hagaman, JR, Kim, HS, Zaika, OL, Mamenko, M, Kayashima, Y, Matsuki, K, Hiller, S, Li, F, Xu, L, Grant, R, Bertorello, AM & Smithies, O 2013, 'Primary aldosteronism and impaired natriuresis in mice underexpressing TGFβ1', Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 14, pp. 5600-5605. https://doi.org/10.1073/pnas.1302641110
Kakoki, Masao ; Pochynyuk, Oleh M. ; Hathaway, Catherine M. ; Tomita, Hirofumi ; Hagaman, John R. ; Kim, Hyung Suk ; Zaika, Oleg L. ; Mamenko, Mykola ; Kayashima, Yukako ; Matsuki, Kota ; Hiller, Sylvia ; Li, Feng ; Xu, Longquan ; Grant, Ruriko ; Bertorello, Alejandro M. ; Smithies, Oliver. / Primary aldosteronism and impaired natriuresis in mice underexpressing TGFβ1. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 14. pp. 5600-5605.
@article{6f01f6317db741149b515b643d883d24,
title = "Primary aldosteronism and impaired natriuresis in mice underexpressing TGFβ1",
abstract = "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.",
keywords = "Hyperthermia, Idiopathic bilateral adrenal hyperplasia",
author = "Masao Kakoki and Pochynyuk, {Oleh M.} and Hathaway, {Catherine M.} and Hirofumi Tomita and Hagaman, {John R.} and Kim, {Hyung Suk} and Zaika, {Oleg L.} and Mykola Mamenko and Yukako Kayashima and Kota Matsuki and Sylvia Hiller and Feng Li and Longquan Xu and Ruriko Grant and Bertorello, {Alejandro M.} and Oliver Smithies",
year = "2013",
month = "4",
day = "2",
doi = "10.1073/pnas.1302641110",
language = "English (US)",
volume = "110",
pages = "5600--5605",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "14",

}

TY - JOUR

T1 - Primary aldosteronism and impaired natriuresis in mice underexpressing TGFβ1

AU - Kakoki, Masao

AU - Pochynyuk, Oleh M.

AU - Hathaway, Catherine M.

AU - Tomita, Hirofumi

AU - Hagaman, John R.

AU - Kim, Hyung Suk

AU - Zaika, Oleg L.

AU - Mamenko, Mykola

AU - Kayashima, Yukako

AU - Matsuki, Kota

AU - Hiller, Sylvia

AU - Li, Feng

AU - Xu, Longquan

AU - Grant, Ruriko

AU - Bertorello, Alejandro M.

AU - Smithies, Oliver

PY - 2013/4/2

Y1 - 2013/4/2

N2 - 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.

AB - 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.

KW - Hyperthermia

KW - Idiopathic bilateral adrenal hyperplasia

UR - http://www.scopus.com/inward/record.url?scp=84875834648&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875834648&partnerID=8YFLogxK

U2 - 10.1073/pnas.1302641110

DO - 10.1073/pnas.1302641110

M3 - Article

C2 - 23503843

AN - SCOPUS:84875834648

VL - 110

SP - 5600

EP - 5605

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 14

ER -