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.
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.
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.
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.
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.
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.
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.
References
Brown, J.J., Chinn, R.H., Gavras, H., Leckie, B., Lever, A.F., McGregor, J., Morton, J.J., Robertson, J.I.S.: Renin and renal function. In: Hypertension '72. J. Genest and E. Koiw (eds.), pp. 81–96. Heidelberg-Berlin-New York, Springer Verlag 1972
Möhring, J., Kohrs, G., Möhring, B., Petri, M., Homsy, E., Haack, D.: Effects of prolonged vasopressin treatment in Brattleboro rats with hereditary diabetes insipidus. Am. J. Physiol., in press (1978)
Ondetti, M.A., Rubin, B., Cushman, D.W.: Design of specific inhibitors of angiotensin-converting enzyme: New Class of orally active antihypertensive agents. Science198, 441–443 (1977)
Oster, P., Hackenthal, E., Hepp, R.: Radioimmunoassay of angiotensin II in rat plasma. Experientia29, 353–354 (1973)
Peters, G., Roch-Ramel, F.: Thiazides and related drugs. In: Handbook of experimental pharmacology, Vol. 14. O. Eichler, A. Farah, H. Herken and A.D. Welch (eds.), pp. 307–313. Berlin-Heidelberg-New York, Springer Verlag 1969
Shirley, D.G., Walter, S.J., Laycock, J.F.: The role of sodium depletion in hydrochlorothiazides-induced antidiuresis in Brattleboro rats with diabetes insipidus. flin. Sci. Mol. Med.54, 209–215 (1978)
Trust, P.M., Brown, J.J., Chinn, R.H., Lever, A.F., Morton, J.J., Padfield, P.L., Robertson, J.I.S., Ireland, J.T., Melville, I.D., Thomson, S.T.: A case of hypopituitarism with diabetes insipidus and loss of thirst. Role of antidiuretic hormone and angiotensin II in the control of urine flow and osmolality. J. Clin. Endocrinol. Metab.41, 346–353 (1975)
Valtin, H., Sawyer, W.B., Sokol, H.W.: Neurohypophyseal principles in rats homozygous and heterozygous for hypothalamic diabetes insipidus. Endocrinology77, 701–706 (1966)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01477455