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

72 Pages Posted: 19 May 2020 Publication Status: Review Complete

See all articles by Johannes Kovarik

Johannes Kovarik

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

Norihiko Morisawa

Kagawa University - Department of Pharmacology

Johannes Wild

Johannes Gutenberg-University Mainz - Division for Cardiology 1

Adriana Marton

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

Kaoru Takase-Minegishi

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

Shintaro Minegishi

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

Steffen Daub

Johannes Gutenberg-University Mainz - Division for Cardiology 1

Jeff M. Sands

Emory University - Department of Medicine

Janet D. Klein

Emory University - Renal Division

James L. Bailey

Emory University - Department of Medicine

Jean-Paul Kovalik

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

Manfred Rauh

Research Laboratory - Division of Paediatrics

Susanne Karbach

Emory University - Department of Medicine

Karl F. Hilgers

University Clinic Erlangen - Division of Nephrology and Hypertension

Friedrich Luft

Max-Delbrück-Center for Molecular Medicine - Experimental and Clinical Research Center

Akira Nishiyama

Kagawa University - Department of Pharmacology

Daisuke Nakano

Kagawa University - Department of Pharmacology

Kento Kitada

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

Jens Titze

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

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Abstract

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 body water. Metabolic aestivation responses to chronic renal failure require nitrogen-rich organic osmolyte production. Continuous endogenous energy and nitrogen supply from skeletal muscle in support of this metabolic requirement explains “renal” muscle mass loss. Accompanying circulatory aestivation responses are designed to limit skin water loss. This process requires vasoconstriction, which explains “renal” hypertension.

Keywords: water conservation, 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

Suggested Citation

Kovarik, Johannes and Morisawa, Norihiko and Wild, Johannes and Marton, Adriana and Takase-Minegishi, Kaoru and Minegishi, Shintaro and Daub, Steffen and Sands, Jeff M. and Klein, Janet D. and Bailey, James L. and Kovalik, Jean-Paul and Rauh, Manfred and Karbach, Susanne and Hilgers, Karl F. and Luft, Friedrich and Nishiyama, Akira and Nakano, Daisuke and Kitada, Kento and Titze, Jens, Aestivation Motifs Explain Hypertension and Muscle Catabolism in Experimental Chronic Renal Failure. Available at SSRN: https://ssrn.com/abstract=3588890 or http://dx.doi.org/10.2139/ssrn.3588890
This version of the paper has not been formally peer reviewed.

Johannes Kovarik

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

8 College Road
169857
Singapore

Norihiko Morisawa

Kagawa University - Department of Pharmacology

Takamatsu
Kagawa 760
United States

Johannes Wild

Johannes Gutenberg-University Mainz - Division for Cardiology 1

Saarstr. 21
Jakob Welder-Weg 4
Mainz, 55122
Germany

Adriana Marton

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

8 College Road
169857
Singapore

Kaoru Takase-Minegishi

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

8 College Road
169857
Singapore

Shintaro Minegishi

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

8 College Road
169857
Singapore

Steffen Daub

Johannes Gutenberg-University Mainz - Division for Cardiology 1

Saarstr. 21
Jakob Welder-Weg 4
Mainz, 55122
Germany

Jeff M. Sands

Emory University - Department of Medicine

United States

Janet D. Klein

Emory University - Renal Division

Atlanta, GA
United States

James L. Bailey

Emory University - Department of Medicine

United States

Jean-Paul Kovalik

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

8 College Road
169857
Singapore

Manfred Rauh

Research Laboratory - Division of Paediatrics

Susanne Karbach

Emory University - Department of Medicine

United States

Karl F. Hilgers

University Clinic Erlangen - Division of Nephrology and Hypertension

Maximiliansplatz 2
Erlangen, 91054
Germany

Friedrich Luft

Max-Delbrück-Center for Molecular Medicine - Experimental and Clinical Research Center

Anna-Louisa-Karsch-Straße 2
Berlin, 10178
Germany

Akira Nishiyama

Kagawa University - Department of Pharmacology

Takamatsu
Kagawa 760
United States

Daisuke Nakano

Kagawa University - Department of Pharmacology

Takamatsu
Kagawa 760
United States

Kento Kitada

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders

8 College Road
169857
Singapore

Jens Titze (Contact Author)

Duke-NUS Graduate Medical School - Programme in Cardiovascular and Metabolic Disorders ( email )

8 College Road
169857
Singapore

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