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

Author(s)

Coelho, Fernanda Oliveira ^[1] ; Jorge, Lecticia Barbosa ^[1] ; de Braganca Viciana, Ana Carolina ^[1] ; Sanches, Talita R. ^[1] ; dos Santos, Fernando ^[2] ; Helou, Claudia M. B. ^[1] ; Irigoyen, Maria Claudia ^[2] ; Kuro-o, Makoto ^[3] ; Andrade, Lucia ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Div Nephrol, Av Dr Arnaldo 455, 3 Andar, Sala 3310, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Heart Inst, Hypertens Unit, Sao Paulo - Brazil

^[3] Jichi Med Univ, Mol Med Dept, Shimotsuke, Tochigi - Japan

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY; v. 314, n. 5, p. F992-F998, MAY 2018.
• Web of Science Citations: 1

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 chinking water, comparing wild-type (WT) mice, klotho-haploinsufficient (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 alpha-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. (AU)

• FAPESP's process: 10/19012-0 - Evaluation of hematopoietic stem cell treatment in dogs with chronic renal failure
• Grantee: Lucia da Conceição Andrade
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/08529-2 - Vitamin D deficiency in oncological critically ill patients
• Grantee: Lucia da Conceição Andrade
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/03025-1 - Pathophysiological study of urinary transporters along the nephron in mice knockout for Klotho gene: The importance of klotho protein in tubular transport, in the acidification mechanisms and in the urinary dilution and concentration
• Grantee: Talita Rojas Cunha Sanches
• Support Opportunities: Scholarships in Brazil - Post-Doctoral