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Inhibition of the renin-angiotensin-system in brattleboro rats with hereditary hypothalamic diabetes insipidus

Hemmung des Renin-Angiotensin-Systems bei Ratten mit hereditärem hypothalamischem Diabetes insipidus

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Zusammenfassung

Bei Brattleboro-Ratten mit hereditärem hypothalamischen Diabetes insipidus (DI Ratten) wurden folgende Fragen untersucht: a) Wirken exogenes and endogenes Angiotensin II (AII) antidiuretisch bei Diabetes insipidus? b) Vermittelt AII den antidiuretischen Effekt von Furosemid? Ergebnisse:

  1. 1.

    AII (5 mg/kg s.c. in Ö1) und Furosemid (50 mg/kg i.p.) verminderten die Urin- und erhöhten die renale Natriumausscheidung. Furosemid führte zu einem zweifachen Anstieg der AII Plasma Konzentration und zur Verminderung der Plasma-Natrium Konzentration.

  2. 2.

    SQ 14 225 (2×2,5 mg/kg p.o.), ein Hemmer des Angiotensin I Converting Enzym, führte zu einer Zunahme der Urin- und der renalen Natriumausscheidung.

  3. 3.

    Auch wenn die Bildung von AII mit SQ 14 225 (2×2,5 mg/kg p.o.) blockiert wurde, reduzierte Furosemid die Urinausscheidung, obwohl die AII Plasma Konzentration 2,5fach vermindert war.

Wir schließen daraus, daß Plasma AII bei DI Ratten antidiuretisch wirken kann. Allerdings vermittelt AII nicht den antidiuretischen Effekt von Furosemid.

Summary

Brattleboro rats homozygous for hypothalamic hereditary diabetes insipidus (DI rats) were used to investigate the following questions: a) Do exogenous and endogenous angiotensin II (AII) have an antidiuretic effect in diabetes insipidus? b) Does AII mediate the antidiuresis induced by furosemide? The following results were obtained:

  1. 1.

    AII (5 mg/kg s.c. in oil) and furosemide (50 mg/kg i.p.) decreased urine flow and increased urinary sodium excretion. Furosemide led to a two-fold increase of AII plasma concentrations and a decrease of plasma sodium levels.

  2. 2.

    SQ 14 225 (2×2.5 mg/kg p.o.), an angiotensin I-converting enzyme inhibitor, led to an increase of urine flow and to a slightly elevated urinary sodium excretion.

  3. 3.

    When the formation of AII was blocked by SQ 14 225 (2×2.5 mg/kg p.o.), AII plasma concentrations were 2.5-fold decreased, but furosemide still reduced urine flow.

We conclude that plasma AII might have an antidiuretic action in DI rats. However, AII does not mediate the antidiuresis induced by furosemide.

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

    J. F. E. Mann M.D., W. Rascher, A. Schömig & R. Dietz

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  1. J. F. E. Mann M.D.
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  2. W. Rascher
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  3. A. Schömig
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  4. R. Dietz
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Mann, J.F.E., Rascher, W., Schömig, A. et al. Inhibition of the renin-angiotensin-system in brattleboro rats with hereditary hypothalamic diabetes insipidus. Klin Wochenschr 56 (Suppl 1), 67–70 (1978). https://doi.org/10.1007/BF01477455

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  • DOI: https://doi.org/10.1007/BF01477455

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