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Role of cyclic AMP in the regulation of renin release from the isolated perfused rat kidney

Wirkung von cyclischem AMP auf die Reninfreisetzung an der isoliert perfundierten Rattenniere

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Zusammenfassung

Die Beteiligung von cyclischem AMP an der Regulation der Reninfreisetzung wurde an isolierten Rattennieren untersucht, die in einem nicht rezirkulierenden System mit einer modifizierten Krebs-Henseleit-Lösung druckkonstant perfundiert wurden. Isoprenalin (IP) (2×10−9 bis 2×10−6 M) und 30-Isobutyl-1-Methyl-Xanthin (IBMX) (4×10−7 bis 7×10−5 M) erhöhten dosisabhängig die Nierendurchströmung, die glomeruläre Filtrationsrate und die Natriumausscheidung. Die Reninfreisetzung stieg bis auf das 10fache der Ausgangswerte an. Während der Infusion der niedrigsten Dosen steigerte IP die Reninfreisetzung ohne die renale Hämodynamik zu beeinflussen. Die gemeinsame Verabreichung von IP und IBMX fürte zu einer supraadditiven Stimulation der Reninfreisetzung. Dibutyryl-cAMP und 8-Br-cGMP (10−6 bis 10−4 M) bewirkten eine gleichartige dosisabhängige Vadodilatation und Natriurese aber unterschieden sich in ihrer Wirkung auf die Reninfreisetzung. Dibutyryl-cAMP stimulierte innerhalb von 15 min die Reninabgabe aus der Niere bis zum 4fa-chen der Kontrollwerte, während 8-Br-cGMP die Reninfreisetzung nicht beeinflußte. Diese Befunde lassen annehmen, daß IP, IBMX und Dibutyryl-cAMP die Reninfreisetzung unabhängig von Änderungen der renalen Hämodynamik und der Natriumausscheidung durch eine Erhöhung der Konzentration von cyclischem AMP in den epitheloiden Zellen beeinflussen.

Summary

The role of cyclic AMP in the regulation of renin release (RR) was studied in isolated rat kidneys, which were perfused at constant pressure in a single-pass system with a modified Krebs-Henseleit solution. Isoproterenol (IP) (2×10−9 to 2×10−6 M) and 3-isobutyl-1-methyl-xanthine (IBMX) (4×10−7 to 7×10−5 M) induced a dose-dependent increase of renal perfusate flow, glomerular filtration rate and urinary sodium excretion. RR was stimulated up to 10-fold above control values within 5 min. At the lowest concentrations IP stimulated RR, but did not affect renal haemodynamics. When IP and IBMX were administered concomitantly, a supraadditive stimulation of RR was observed. Dibutyryl-cAMP (db-cAMP) and 8-Br-cGMP (10−6 to 10−4 M) produced a similar dose-dependent vasodilation and natriuresis, but differed in their action on RR. Within 15 min after the start of the infusion, db-cAMP increased RR up to 4-fold, whereas 8-Br-cGMP was without an effect. These results suggest that IP, IBMX and db-cAMP stimulated RR by increasing the concentrations of cAMP in the epitheloid cells and independently of changes in renal haemodynamics and sodium excretion.

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Authors and Affiliations

  1. Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, D-6900, Heidelberg, Federal Republic of Germany

    K. G. Hofbauer M.D., A. Konrads, K. Schwarz & U. Werner

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  1. K. G. Hofbauer M.D.
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  2. A. Konrads
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  3. K. Schwarz
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  4. U. Werner
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Hofbauer, K.G., Konrads, A., Schwarz, K. et al. Role of cyclic AMP in the regulation of renin release from the isolated perfused rat kidney. Klin Wochenschr 56 (Suppl 1), 51–59 (1978). https://doi.org/10.1007/BF01477453

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  • DOI: https://doi.org/10.1007/BF01477453

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