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Interactions of diuretics with the renal kallikrein-kinin and prostaglandin systems

Interaktionen von Diuretika mit den renalen Kallikrein-Kinin- und Prostaglandin-Systemen

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Summary

The renal kallikrein-kinin system may participate in the diuretic, natriuretic and antihypertensive effect of diuretics. This possibility was investigated by studying the influence of hydrochlorothiazide on blood pressure and urinary kallikrein excretion in patients with essential hypertension. Furthermore, the effect of kallikrein-blockade and prostaglandin-synthesis inhibition on the acute furosemide-induced changes of diuresis, natriuresis, GFR and renal plasma flow were studied in normotensive subjects. Thiazide treatment normalized the reduced kallikrein excretion of the hypertensive patients. The fall in mean arterial blood pressure was significantly correlated with the increase in urinary kallikrein excretion. In the normotensive subjects aprotinin-induced kallikrein inhibition failed to alter the acute response to furosemide, whereas indomethacin attenuated the diuretic and natriuretic effect of furosemide. The combination of indomethacin and aprotinin had a greater suppressive effect on plasma renin activity than indomethacin alone, suggesting a participation of kallikrein in renin release. An increase in the activity of the renal kallikreinkinin system may contribute to the long-term antihypertensive effect of thiazide diuretics but it does not seem to be involved in the acute renal responses to furosemide.

Zusammenfassung

Das renale Kallikrein-Kinin System ist möglicherweise am diuretischen, natriuretischen und antihypertensiven Effekt von Diuretika beteiligt. In der vorliegenden Studie wurde deshalb an Patienten mit essentieller Hypertension der Einfluß von Hydrochlorothiazid auf das Blutdruckverhalten und die renale Kallikreinaktivität untersucht. Zusätzlich wurde bei Normalpersonen die Beeinflußbarkeit der renalen Furosemidwirkung durch Kallikreinblockade und Hemmung der Prostaglandinsynthese gemessen.

Hydrochlorothiazidbehandlung normalisierte die erniedrigte Kallikreinausscheidung hypertensiver Patienten. Der Abfall des mittleren arteriellen Drucks korrelierte mit dem Anstieg der Kallikreinausscheidung. Bei den normotensiven Probanden wurden die akuten Furosemid-induzierten Änderungen von Diurese, Natriurese, glomerulärer Filtration und renalem Plasmafluß durch Kallikreinhemmung mit Aprotinin nicht beeinflußt. Indomethacin hingegen verminderte den diuretischen und natriuretischen Effekt von Furosemid. Die Plasmareninaktivität wurde durch die Kombination von Indomethacin und Aprotinin deutlicher supprimiert als durch Indomethacin allein. Dies könnte auf eine Beteiligung von Kallikrein an der Reninfreisetzung hinweisen. Eine Aktivitätszunahme des renalen Kallikrein-Kinin Systems könnte zum antihypertensiven Effekt der Thiaziddiuretika beitragen. Andererseits scheint dieses System an den akuten renalen Wirkungen von Furosemid nicht beteiligt zu sein.

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Authors and Affiliations

  1. Medizinische Universitäts-Poliklinik, Wilhelmstr. 35, D-5300, Bonn 1, Germany

    A. Overlack, K. O. Stumpe, H. -M. Müller, R. Kolloch & M. Higuchi

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  1. A. Overlack
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  2. K. O. Stumpe
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  3. H. -M. Müller
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  4. R. Kolloch
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  5. M. Higuchi
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Dedicated to Professor F. Krück on the occasion of his 60th birthday

Supported in part by the Ministerium für Wissenschaft und Forschung, Nordrhein-Westfalen (Grant No. IV B5-FA 8421)

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Overlack, A., Stumpe, K.O., Müller, H.M. et al. Interactions of diuretics with the renal kallikrein-kinin and prostaglandin systems. Klin Wochenschr 60, 1223–1228 (1982). https://doi.org/10.1007/BF01716727

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