【7/12更新】2022年4月1日からのCiNii ArticlesのCiNii Researchへの統合について

Na+-Cl− cotransporter-mediated chloride uptake contributes to hypertension and renal damage in aldosterone-infused rats

  • Takahiro Yamauchi
    Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
  • Shigehiro Doi
    Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
  • Ayumu Nakashima
    Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
  • Toshiki Doi
    Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
  • Eisei Sohara
    Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
  • Shinichi Uchida
    Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
  • Takao Masaki
    Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan

抄録

<jats:p> Recently, in addition to epithelial sodium channel alpha-subunit (αENaC), the thiazide-sensitive sodium-chloride cotransporter (NCC) and pendrin, also known as sodium-independent chloride/iodide transporter, were reported to be activated by aldosterone. Here, we investigated whether chloride (Cl<jats:sup>−</jats:sup>) is responsible for hypertension, inflammation, and renal damage in aldosterone-infused rats. Following left nephrectomy, 8-wk-old male Sprague-Dawley rats were allocated into four groups: 1) drinking 1.0% sodium chloride solution with aldosterone infusion (Aldo/NaCl rats); 2) drinking 1.44% sodium bicarbonate solution with aldosterone infusion (Aldo/NaHCO<jats:sub>3</jats:sub> rats); 3) drinking distilled water with aldosterone infusion (Aldo/water rats); and 4) drinking distilled water without aldosterone infusion (sham rats). Additionally, heminephrectomized rats with aldosterone infusion were fed a 0.26% NaCl diet (control); 8.0% NaCl diet (high-Na/high-Cl); or a 4.0% NaCl 6.67% sodium citrate diet (high-Na/half-Cl). Last, Aldo/NaCl rats were treated with or without hydrochlorothiazide. Blood pressure in the Aldo/NaCl rats was significantly higher than in the Aldo/NaHCO<jats:sub>3</jats:sub> rats, which was associated with the increased expression of NCC. Expression of markers of inflammation (CD3, CD68, interleukin-17A) and fibrosis (α-smooth muscle actin, collagen 1) were also increased in Aldo/NaCl rats. Similarly, aldosterone-infused rats fed a high-Na/half-Cl diet had lower blood pressure than those fed a high-Na/high-Cl diet, with a reduction of phosphorylated NCC, but not αENaC and pendrin. NCC inhibition with hydrochlorothiazide attenuated interleukin-17A protein expression along with the phosphorylation of NCC in Aldo/NaCl rats. These findings suggest that NCC-mediated Cl<jats:sup>−</jats:sup> uptake plays important roles in the development of aldosterone-induced hypertension and renal injury. </jats:p>

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