0000000000174781

AUTHOR

Manfred Rauh

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

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‐hour metabolic cage experiments, chronic blood pressure by radiotelemetry, chronic metabolic adjustment in liver and skeletal muscle by metabolomics and selected enzyme activity…

research product

Aestivation Motifs Explain Hypertension and Muscle Catabolism in Experimental Chronic Renal Failure

Chronic renal failure leads to muscle mass loss and hypertension, which according to textbook teaching occur secondary to an inability of the kidneys to excrete solutes and water. We found instead that rats with experimental chronic renal failure constantly lost body water, because their kidneys could not sufficiently concentrate the urine. Physiological adaptation to body water loss, termed aestivation, is an evolutionary conserved survival strategy that relies on complex physiologic-metabolic adjustment across multiple organs to prevent otherwise lethal dehydration. We show that rats with chronic renal failure utilize these ancient water conservation motifs to successfully stabilize their…

research product

Aestivation motifs explain hypertension and muscle mass loss in mice with psoriatic skin barrier defect

Aim Recent evidence suggests that arterial hypertension could be alternatively explained as a physiological adaptation response to water shortage, termed aestivation, which relies on complex multi-organ metabolic adjustments to prevent dehydration. Here, we tested the hypothesis that chronic water loss across diseased skin leads to similar adaptive water conservation responses as observed in experimental renal failure or high salt diet. Methods We studied mice with keratinocyte-specific overexpression of IL-17A which develop severe psoriasis-like skin disease. We measured transepidermal water loss and solute and water excretion in the urine. We quantified glomerular filtration rate (GFR) by…

research product