TY - JOUR
T1 - Chronic nicotine exposure reduces klotho expression and triggers different renal and hemodynamic responses in klotho-haploinsufficient mice
AU - Coelho, Fernanda Oliveira
AU - Jorge, Lecticia Barbosa
AU - de Bragança Viciana, Ana Carolina
AU - Sanches, Talita R.
AU - dos Santos, Fernando
AU - Helou, Claudia M.B.
AU - Irigoyen, Maria Claudia
AU - Kuro-o, Makoto
AU - Andrade, Lucia
N1 - Publisher Copyright:
© 2018 the American Physiological Society.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Baroreflex sensitivity
KW - Glomerular filtration rate
KW - Klotho
KW - Nicotine
KW - Sympathetic modulation
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U2 - 10.1152/ajprenal.00442.2016
DO - 10.1152/ajprenal.00442.2016
M3 - Article
C2 - 29363324
AN - SCOPUS:85059904972
SN - 1931-857X
VL - 314
SP - F992-F998
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 5
ER -