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  • The first proof-of-concept model of salt-sensitive hypertension due to “pure” renal dysfunction

RCAST Report

The first proof-of-concept model of salt-sensitive hypertension due to “pure” renal dysfunction


The first proof-of-concept study about the importance of renal dysfunction on developing salt-sensitive hypertension by project researcher Kohei Ueda and Emeritus Professor Toshiro Fujita at Research Center for Advanced Science and Technology, The University of Tokyo was published online in Hypertension.

Hypertension is a major risk factor of cardiovascular diseases in Japan and excessive salt intake is well-known to play an important role in developing hypertension. Renal dysfunction has been accepted as the essential mechanism of salt-sensitive hypertension, because renal dysfunction leads to insufficient urinary excretion of salt and to elevating blood pressure. This “renal dysfunction theory”, so-called Guyton’s theory, was recently criticized for the lack of evidence that “pure” renal dysfunction initiates hypertension.

To approach this question, the team generated kidney-specific knockout mice of Hsd11b2 gene, which regulates appropriate reabsorptions of salt in the kidney. The team demonstrated that pure renal dysfunction in the mice caused hypertension and hypokalemia, main symptoms of the inherited disorder with Hsd11b2 gene mutation, apparent mineralocorticoid excess (AME), and revealed the mechanism of hypertension attributed to hypokalemia-induced activation of Na+-Cl- cotransporter, following to activation of epithelial Na+ channel in the kidney. This animal is the first proof-of-concept model of not only AME but also salt-sensitive hypertension caused by pure renal dysfunction.


別ウィンドウで開く 『Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension

Kohei Ueda, Mitsuhiro Nishimoto, Daigoro Hirohama, Nobuhiro Ayuzawa, Wakako Kawarazaki, Atsushi Watanabe, Tatsuo Shimosawa, Johannes Loffing, Ming-Zhi Zhang, Takeshi Marumo, Toshiro Fujita

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