Abstract
The 24 h-course of plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma corticosterone concentration (PCC) and of the urinary excretion of sodium, potassium and aldosterone was investigated in male Sprague-Dawley rats under different experimental conditions. The data obtained can be summarized as follows:
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1.
The renin-angiotensin-aldosterone system (RAAS) of the rat is subject to a circadian rhythm which is largely in phase with the well-known rhythm of the pituitary-adrenal axis. This rhythm can be demonstrated in PRA as well as in plasma concentrations and urinary excretion rates of aldosterone. The rhythm of urinary excretion of electrolytes is unlikely to be due to the rhythm of aldosterone secretion.
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2.
The light-dark cycle is the main synchronizer for these rhythms: inverting the light-dark cycle for 5 weeks entirely inverts the rhythms of all the parameters cited.
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3.
A dissociation of the rhythms of PRA and PAC can be observed following sodium restriction or dexamethasone treatment. A role of ACTH in regulating the rhythmic pattern of aldosterone secretion is suggested by the finding that PAC and PCC follow the same pattern of circadian variations under every experimental condition tested.
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4.
The responsiveness of the RAAS to stimulation or suppression varies with the time of day.
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5.
It is suggested that experiments ought to be performed not only during the inactive (light hours) but also during the active (dark hours) phase when investigating the RAAS in the rat. This can conveniently be achieved by the use of an animal room with a reversed lighting regime.
Zusammenfassung
Der 24 Std-Verlauf der Plasma-Renin-Aktivität (PRA), der Plasma-Aldosteron-Konzentration (PAC), der Plasma-Corticosteron-Konzentration (PCC) sowie der Urinexkretion von Natrium, Kalium und Aldosteron wurde an männlichen Sprague-Dawley-Ratten unter verschiedenen experimentellen Bedingungen untersucht. Die Ergebnisse lassen sich wie folgt zusammenfassen:
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1.
Das Renin-Angiotensin-Aldosteron-System (RAAS) der Ratte weist einen zirkadianen Rhythmus auf, der dem gut bekannten Rhythmus des Hypophysen Nebennierenrinden-Systems parallel läuft. Dieser Rhythmus läßt sich durch Messung der PRA, der PAC und der Exkretionsrate von Aldosteron im Urin nachweisen. Der Rhythmus der Elektrolytausscheidung im Urin scheint nicht durch den Rhythmus der Aldosteronsekretion bedingt zu sein.
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2.
Der Licht-Dunkel-Zyklus ist der Zeitgeber für diese Rhythmen: Eine Umkehr des Licht-Dunkel-Zyklus für 5 Wochen bewirkt eine komplette Umkehr der Rhythmen aller genannten Parameter.
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3.
Unter Natrium-Restriktion oder Dexamethason-Behandlung wird eine Dissoziation des Rhythmus der PRA von dem der PAC beobachtet, während der Rhythmus der PAC unter allen Versuchsbedingungen mit dem der PCC parallel geht. Diese Beobachtung legt den Schluß nahe, daß das ACTH an der Steuerung des Rhythmus der Aldosteronsekretion beteiligt ist.
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4.
Der Grad der Stimulierbarkeit bzw. Supprimierbarkeit des RAAS unterliegt tageszeitlichen Schwankungen.
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5.
Es wird daher empfohlen, bei Untersuchungen über das RAAS der Ratte die Experimente nicht nur während der Inaktivitätsperiode (Lichtphase), sondern auch während der Aktivitätsperiode (Dunkelphase) dieser Tiere durchzuführen. Dies läßt sich durch Benutzung eines Tierstalls mit umgekehrtem Licht-DunkelZyklus vereinfachen.
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Read at the Symposium “Relevance of Chronobiology for Toxicology and Pharmacology” held at the 16th Spring Meeting of the Deutsche Pharmakologische Gesellschaft, Section: Toxicology, March 6, 1975, Mainz
The excellent technical assistance of Miss E. Hempen and Mrs. S. Henke is gratefully acknowledged.
This study was supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 146, C 5.
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Hilfenhaus, M. Circadian rhythm of the renin-angiotensin-aldosterone system in the rat. Arch. Toxicol. 36, 305–316 (1976). https://doi.org/10.1007/BF00340536
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DOI: https://doi.org/10.1007/BF00340536