Chronic nicotine exposure reduces klotho expression and triggers different renal and hemodynamic responses in klotho-haploinsufficient mice

Fernanda Oliveira Coelho, Lecticia Barbosa Jorge, Ana Carolina de Bragança Viciana, Talita R. Sanches, Fernando dos Santos, Claudia M.B. Helou, Maria Claudia Irigoyen, Makoto Kuro-o, Lucia Andrade

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The klotho gene, which encodes a single-pass transmembrane protein and a secreted protein, is expressed predominantly by the distal renal tubules and is related to calcium phosphorus metabolism, ion channel regulation, intracellular signaling pathways, and longevity. Klotho deficiency aggravates acute kidney injury and renal fibrosis. Exposure to nicotine also worsens kidney injury. Here, we investigated renal Klotho protein expression in a mouse model of chronic (28-day) nicotine exposure, in which mice received nicotine or vehicle (saccharine) in drinking water, comparing wild-type (WT) mice, klothohaploinsufficient (kl/+) mice, and their respective controls, in terms of the effects of that exposure. Nicotine exposure was associated with a significant decline in renal Klotho expression in WT and kl/+ mice as well as a reduction in the glomerular filtration rate in WT mice. Although plasma electrolytes were similar among the groups, fractional excretion of sodium was reduced in both nicotine-exposed groups. The nicotine-WT mice presented augmented baroreflex sensitivity to nitroprusside and augmented sympathetic cardiac modulation. However, nicotine-kl/+ mice presented higher plasma levels of urea and aldosterone together with a higher α-index (spontaneous baroreflex) and higher peripheral sympathetic modulation, as evaluated by spectral analysis. We can conclude that nicotine downregulates Klotho expression as well as that renal and autonomic responses to nicotine exposure are modified in kl/+ mice.

Original languageEnglish (US)
Pages (from-to)F992-F998
JournalAmerican Journal of Physiology - Renal Physiology
Volume314
Issue number5
DOIs
StatePublished - 2018

Keywords

  • Baroreflex sensitivity
  • Glomerular filtration rate
  • Klotho
  • Nicotine
  • Sympathetic modulation

ASJC Scopus subject areas

  • Physiology
  • Urology

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    Coelho, F. O., Jorge, L. B., de Bragança Viciana, A. C., Sanches, T. R., dos Santos, F., Helou, C. M. B., Irigoyen, M. C., Kuro-o, M., & Andrade, L. (2018). Chronic nicotine exposure reduces klotho expression and triggers different renal and hemodynamic responses in klotho-haploinsufficient mice. American Journal of Physiology - Renal Physiology, 314(5), F992-F998. https://doi.org/10.1152/ajprenal.00442.2016