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Renal renin secretion as regulator of body fluid homeostasis

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Abstract

The renin–angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium intake, but the specific pathways involved and the relations between them are not well defined. In animals, renin secretion is a log-linear function of sodium intake. Close associations exist between sodium intake, total body sodium, extracellular fluid volume, and blood volume. Plasma volume increases by about 1.5 mL/mmol increase in daily sodium intake. Several lines of evidence indicate that central blood volume may vary substantially without measurable changes in arterial blood pressure. At least five intertwining feedback loops of renin regulation are identifiable based on controlled variables (blood volume, arterial blood pressure), efferent pathways to the kidney (nervous, humoral), and pathways operating via the macula densa. Taken together, the available evidence favors the notion that under physiological conditions (1) volume-mediated regulation of renin secretion is the primary regulator, (2) macula densa mediated mechanisms play a substantial role as co-mediator although the controlled variables are not well defined so far, and (3) regulation via arterial blood pressure is the exception rather than the rule. Improved quantitative analyses based on in vivo and in silico models are warranted.

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Notes

  1. It is often stated that the fraction of plasma osmolality generated by sodium salts is above 90 %, even 95 %. A representative value for [Na+] in plasma (plasma water) is 142 mmol/L (151 mmol/L). However, a significant part is associated with protein anions, so that the total molar concentration in plasma of cations is 149.5 mmol/L and of anions is 137.5 mmol/L [1] providing a molar ratio of 0.867. The osmotic coefficient for Na+ (as chloride) at the ionic strength of plasma is close to 0.91. The osmolality of Na+ and (mainly chloride) anions in plasma water can thus be calculated to be near 257 mOsm/kg. Plasma osmolality is close to 290 mOsm/kg. Therefore, sodium and associated anions account for some 88 % of plasma osmolality.

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Acknowledgments

The work of the authors has been supported by Novo Nordisk Foundation (PB), Danish Heart Association (PB), and the Danish Medical Research Council (GLI).

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Authors and Affiliations

  1. Department of Paediatrics, Kolding Hospital, Kolding, Denmark

    Mads Damkjær

  2. Institute of Molecular Medicine, University of Southern Denmark, 21 J.B. Winsloews Vej, 5000, Odense, Denmark

    Gustaf L. Isaksson, Jane Stubbe, Boye L. Jensen, Kasper Assersen & Peter Bie

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Correspondence to Peter Bie.

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This article is published as part of the special issue on the Renin–Angiotensin System.

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Damkjær, M., Isaksson, G.L., Stubbe, J. et al. Renal renin secretion as regulator of body fluid homeostasis. Pflugers Arch - Eur J Physiol 465, 153–165 (2013). https://doi.org/10.1007/s00424-012-1171-2

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  • DOI: https://doi.org/10.1007/s00424-012-1171-2

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