0000000000174791

AUTHOR

Karl F. Hilgers

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…

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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…

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Practical solutions to the challenges of uncontrolled hypertension: a white paper.

This white paper is an urgent call to action from aninternational group of physicians. The continued failure tocontrolhypertensiontakesanunacceptabletollon patients,families and society and it must be addressed. Any patientwith blood pressure of 140/90 mmHg or greater can becharacterizedasa ‘challengingpatient’,is atsignificant risk,and requires persistent optimization of therapy until targetblood pressure is achieved. Six key challenges in reachingthis goal blood pressure are described: (1) inadequateprimary prevention; (2) faulty awareness of risk; (3) lack ofsimplicity; (4) therapeutic inertia; (5) insufficient patientempowerment; and (6) unsupportive healthcare systems.This white paper id…

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