Tags

Type your tag names separated by a space and hit enter

Na+-Cl- cotransporter-mediated chloride uptake contributes to hypertension and renal damage in aldosterone-infused rats.
Am J Physiol Renal Physiol. 2018 08 01; 315(2):F300-F312.AJ

Abstract

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-) 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/NaHCO3 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/NaHCO3 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- uptake plays important roles in the development of aldosterone-induced hypertension and renal injury.

Authors+Show Affiliations

Department of Nephrology, Hiroshima University Hospital , Hiroshima , Japan.Department of Nephrology, Hiroshima University Hospital , Hiroshima , Japan.Department of Nephrology, Hiroshima University Hospital , Hiroshima , Japan.Department of Nephrology, Hiroshima University Hospital , Hiroshima , Japan.Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo , Japan.Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo , Japan.Department of Nephrology, Hiroshima University Hospital , Hiroshima , Japan.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29631358

Citation

Yamauchi, Takahiro, et al. "Na+-Cl- Cotransporter-mediated Chloride Uptake Contributes to Hypertension and Renal Damage in Aldosterone-infused Rats." American Journal of Physiology. Renal Physiology, vol. 315, no. 2, 2018, pp. F300-F312.
Yamauchi T, Doi S, Nakashima A, et al. Na+-Cl- cotransporter-mediated chloride uptake contributes to hypertension and renal damage in aldosterone-infused rats. Am J Physiol Renal Physiol. 2018;315(2):F300-F312.
Yamauchi, T., Doi, S., Nakashima, A., Doi, T., Sohara, E., Uchida, S., & Masaki, T. (2018). Na+-Cl- cotransporter-mediated chloride uptake contributes to hypertension and renal damage in aldosterone-infused rats. American Journal of Physiology. Renal Physiology, 315(2), F300-F312. https://doi.org/10.1152/ajprenal.00504.2016
Yamauchi T, et al. Na+-Cl- Cotransporter-mediated Chloride Uptake Contributes to Hypertension and Renal Damage in Aldosterone-infused Rats. Am J Physiol Renal Physiol. 2018 08 1;315(2):F300-F312. PubMed PMID: 29631358.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Na+-Cl- cotransporter-mediated chloride uptake contributes to hypertension and renal damage in aldosterone-infused rats. AU - Yamauchi,Takahiro, AU - Doi,Shigehiro, AU - Nakashima,Ayumu, AU - Doi,Toshiki, AU - Sohara,Eisei, AU - Uchida,Shinichi, AU - Masaki,Takao, Y1 - 2018/04/04/ PY - 2018/4/11/pubmed PY - 2019/7/10/medline PY - 2018/4/11/entrez KW - aldosterone KW - chloride KW - hypertension KW - inflammation KW - sodium-chloride cotransporter SP - F300 EP - F312 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 315 IS - 2 N2 - 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-) 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/NaHCO3 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/NaHCO3 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- uptake plays important roles in the development of aldosterone-induced hypertension and renal injury. SN - 1522-1466 UR - https://www.unboundmedicine.com/medline/citation/29631358/Na+_Cl__cotransporter_mediated_chloride_uptake_contributes_to_hypertension_and_renal_damage_in_aldosterone_infused_rats_ L2 - http://www.physiology.org/doi/full/10.1152/ajprenal.00504.2016?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -