Chronic nicotine exposure reduces klotho expression and triggers different renal and hemodynamic responses in klotho-haploinsufficient mice
| Autor: | Lectícia Barbosa Jorge, Lucia Andrade, Fernando dos Santos, Fernanda Oliveira Coelho, Claudia M. B. Helou, Talita Rojas Sanches, Ana Carolina de Braganca Viciana, Makoto Kuro-o, Maria Claudia Irigoyen |
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| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_specialty
Nicotine Fractional excretion of sodium Mice 129 Strain Sympathetic Nervous System Time Factors Physiology 030232 urology & nephrology Renal function Down-Regulation Mice Transgenic Haploinsufficiency 030204 cardiovascular system & hematology Baroreflex urologic and male genital diseases Kidney 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Renal fibrosis Animals Urea Nicotinic Agonists Cotinine Klotho Aldosterone Klotho Proteins HEMODINÂMICA Glucuronidase Chemistry Sodium Acute kidney injury Hemodynamics Heart medicine.disease Renal Elimination Endocrinology Phenotype medicine.drug Glomerular Filtration Rate |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | 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, 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 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. |
| Databáze: | OpenAIRE |
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