Adaptive physiological water conservation explains hypertension and muscle catabolism in experimental chronic renal failure
Open Access
- 16 February 2021
- journal article
- research article
- Published by Wiley in Acta Physiologica
- Vol. 232 (1), e13629
- https://doi.org/10.1111/apha.13629
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
Funding Information
- Austrian Science Fund
- Astellas Foundation for Research on Metabolic Disorders
- Japan Heart Foundation
- Japan Society for the Promotion of Science (19K17889)
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Uehara Memorial Foundation
- National Heart, Lung, and Blood Institute (RO1 HL118579)
This publication has 105 references indexed in Scilit:
- Immune cells control skin lymphatic electrolyte homeostasis and blood pressureJCI Insight, 2013
- Mechanisms and modifiers of reflex induced cutaneous vasodilation and vasoconstriction in humansJournal of Applied Physiology, 2010
- Mononuclear Phagocyte System Depletion Blocks Interstitial Tonicity-Responsive Enhancer Binding Protein/Vascular Endothelial Growth Factor C Expression and Induces Salt-Sensitive Hypertension in RatsHypertension, 2010
- Up‐regulation of arginase activity contributes to attenuated reflex cutaneous vasodilatation in hypertensive humansJournal Of Physiology-London, 2007
- Mobilization of osmotically inactive Na+ by growth and by dietary salt restriction in ratsAmerican Journal of Physiology-Renal Physiology, 2007
- Increases in urea synthesis and the ornithine-urea cycle capacity in the giant African snail,Achatina fulica, during fasting or aestivation, or after the injection with ammonium chlorideJournal of Experimental Zoology Part A: Comparative Experimental Biology, 2005
- Resting and maximal forearm skin blood flows are reduced in hypertension.Hypertension, 1992
- Water permeability of biological membranes Lessons from antidiuretic hormone-responsive epitheliaBiochimica et Biophysica Acta (BBA) - Reviews on Biomembranes, 1982
- Salt, volume and the prevention of hypertension.Circulation, 1976
- Effect of the Antidiuretic Hormone (Pitressin®) on the Insensible Water Loss of the Skin*Journal of Investigative Dermatology, 1956