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Adaptive physiological water conservation explains hypertension and muscle catabolism in experimental chronic renal failure

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Item Type:Article
Title:Adaptive physiological water conservation explains hypertension and muscle catabolism in experimental chronic renal failure
Creators Name:Kovarik, J. and Morisawa, N. and Wild, J. and Marton, A. and Takase-Minegishi, K. and Minegishi, S. and Daub, S. and Sands, J.M. and Klein, J.D. and Bailey, J.L. and Kovalik, J.P. and Rauh, M. and Karbach, S. and Hilgers, K.F. and Luft, F. and Nishiyama, A. and Nakano, D. and Kitada, K. and Titze, J.
Abstract:AIM: We have reported earlier that a high salt intake triggered an aestivation-like natriuretic-ureotelic body water conservation response that lowered muscle mass and increased blood pressure. Here we tested the hypothesis that a similar adaptive water conservation response occurs in experimental chronic renal failure. METHODS: In four subsequent experiments in Sprague Dawley rats, we used surgical 5/6 renal mass reduction (5/6 Nx) to induce chronic renal failure. We studied solute and water excretion in 24-h metabolic cage experiments, chronic blood pressure by radiotelemetry, chronic metabolic adjustment in liver and skeletal muscle by metabolomics and selected enzyme activity measurements, body Na(+) , K(+) , and water by dry ashing, and acute transepidermal water loss in conjunction with skin blood flow and intra-arterial blood pressure. RESULTS: 5/6 Nx rats were polyuric, because their kidneys could not sufficiently concentrate the urine. Physiological adaptation to this renal water loss included mobilization of nitrogen and energy from muscle for organic osmolyte production, elevated norepinephrine and copeptin levels with reduced skin blood flow, which by means of compensation reduced their transepidermal water loss. This complex physiologic-metabolic adjustment across multiple organs allowed the rats to stabilize their body water content despite persisting renal water loss, albeit at the expense of hypertension and catabolic mobilization of muscle protein. CONCLUSION: Physiological adaptation to body water loss, termed aestivation, is an evolutionary conserved survival strategy and an under-studied research area in medical physiology, which besides hypertension and muscle mass loss in chronic renal failure may explain many otherwise unexplainable phenomena in medicine.
Keywords:Aestivation, Dehydration, Hypertension, Muscle Mass Loss, Organic Osmolytes, Glycine, Methylation, Urea Cycle, Purine Metabolism, Transamination, Glucose-Alanine-Shuttle, Kidney, Liver, Skin, Urine Concentration, Transepidermal Water Loss, Body Sodium, Body Water, Hepato-Renal, Double-Barrier, Concept, Animals, Rats
Source:Acta Physiologica
ISSN:1748-1708
Publisher:Wiley
Volume:232
Number:1
Page Range:e13629
Date:May 2021
Official Publication:https://doi.org/10.1111/apha.13629
PubMed:View item in PubMed

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