Ciclosporin-induced hypertension is associated with increased sodium transporter of the loop of Henle (NKCC2)

Cristina Esteva-Font, Elisabet Ars, Elena Guillen-Gomez, Josep Maria Campistol, Laia Sanz, Wladimiro Jiménez, Mark Alan Knepper, Ferran Torres, Roser Torra, José Aurelio Ballarín, Patricia Fernández-Llama

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37 Citations (Scopus)


Background. Hypertension induced by cyclosporine is associated with renal sodium and water retention. Using immunoblotting of kidney homogenates, we investigated the regulation of sodium and water transport proteins in a rat model of cyclosporine-induced hypertension. Methods. Rats were treated with cyclosporine (25 mg/kg/day intraperitoneally) during 7 days. Control rats received vehicle. Results. Cyclosporine-treated rats had an increase in blood pressure with a decrease in renal sodium excretion compared with control rats. There were no differences either in sodium intake or in plasma creatinine levels between the two groups of rats. These data suggest that the decrease in sodium excretion in the cyclosporine-treated rats was due to an increase in renal sodium absorption. The densitometric analysis of the renal immunoblot showed an increase in the Na-K-2Cl cotransporter of the loop of Henle (NKCC2) in cyclosporine-treated rats (178% ± 36) compared with control rats (100% ± 18; P < 0.05*). This protein rise was associated with an increase in the NKCC2 mRNA pointing to a transcriptional regulation of this sodium transporter. There were no statistically significant changes in the sodium proton exchange (NHE-3) of the proximal tubule although in this renal segment, aquaporin-1 was increased in cyclosporine-treated rats compared with control rats (control 100% ± 6 vs cyclosporine 119% ± 6; P < 0.05*). Conclusions. Our results pointed to the thick ascending limb of the loop of Henle as an important site of sodium retention in cyclosporine-induced hypertension. This data may have potential clinical implications for the treatment of hypertension induced by cyclosporine. © The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Original languageEnglish
Pages (from-to)2810-2816
JournalNephrology Dialysis Transplantation
Issue number10
Publication statusPublished - 1 Oct 2007


  • Aquaporins
  • Cyclosporine
  • Hypertension
  • NHE-3
  • NKCC2
  • Renal sodium transporters


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