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Untersuchungen zur antihypertensiven Wirkung von Spironolactone

Antihypertensive effect of spironolactone

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Summary

1. The study was designed to demonstrate the antihypertensive mechanism of spironolactone. In 18 patients with benign essential hypertension blood volume, plasma renin activity (PRA) and catecholamine excretion in urine were measured and related to the blood pressure during treatment with placebo and with 100, 200 and 400 mg spironolactone daily.

2. During treatment a dose dependent blood pressure decrease from 176.8 ± 4.9 mm Hg systolic and 118.2 ± 3.0 mm Hg diastolic to 155.0 ± 5.7 mm Hg systolic and 109.1 ± 3.6 mm Hg diastolic with 400 mg spironolactone/d was observed.

3. The blood volume was diminished from 32.14 ± 1.6 ml/cm to 27.96 ± 1.2 ml/cm dose dependently.

4. PRA during rest and after stimulation with 40 mg furosemide intravenously rose dose-dependently during spironolactone treatment.

In 6 of 18 patients PRA was found to be low during recumbency and following stimulation. In these patients the decrease of blood pressure during treatment with 400 mg spironolactone/d was greater than in the other group (p<0.05). The increase of plasma renin activitiy during treatment was similar in both groups.

5. The urinary excretion of norepinephrine increased dose-dependently during treatment but the excretion of vanillin mandelic acid and of epinephrine did not change in a significant.

6. With statistical analysis no significant correlation could be detected between the decrease of blood pressure and PRA in the placebo period. Futhermore, no significant correlation could be observed between decrease of blood pressure and change of PRA or blood volume during treatment.

7. It is discussed that the blood pressure lowering effect of blood volume diminution during spironolactone treatment may be modified by different counterregulation mechanisms.

Zusammenfassung

1. Es wird über Untersuchungen zum antihypertensiven Wirkungsmechanismus von Spironolactone berichtet. Hierzu wurde bei 18 Patienten mit benigner, essentieller Hypertonie das Blutvolumen, die Plasmareninaktivität sowie die Katecholaminausscheidung im Urin während der Behandlung mit einem Placebo und mit 100, 200 und 400 mg Spironolactone/Tag gemessen und in Beziehung zur Blutdrucksenkung gesetzt.

2. Während der Behandlung kam es zu einer dosisabhängigen Blutdrucksenkung von 176,8 ± 4,9 mm Hg syst. und 118,2 ± 3,0 mm Hg diast. auf 155,0 ± 5,7 mm Hg syst. und 109,1 ± 3,6 mm Hg diast. bei Gabe von 400 mg Spironolactone/Tag.

3. Das Blutvolumen verminderte sich ebenfalls dosisabhängig von 32,14 ± 1,6 ml/cm auf 27,96 ± 1,2 ml/cm.

4. Die PRA in Ruhe und nach Stimulation mit 40 mg Furosemid i.v. stieg dosisabhängig an.

Bei 6 von 18 Patienten war die Ausgangs-PRA niedrig und nur gering stimulierbar. Bei diesen Patienten war die Senkung des Blutdruckes bei Gabe von 400 mg Spironolactone/Tag stärker ausgeprägt als bei den anderen Patienten (p<0,05). Der Anstieg der PRA während der Behandlung war in beiden Patientengruppen gleichsinnig.

5. Die Ausscheidung von Noradrenalin im Harn stieg dosisabhängig während der Behandlung an, dagegen änderte sich die Ausscheidung der VMS und Adrenalin nicht signifikant.

6. Bei den statistischen Analysen zeigte sich, daß keine signifikanten Korrelationen bestanden zwischen der Blutdrucksenkung und der Ausgangs-PRA, sowie der Änderung der PRA und der Änderung des Blutvolumens während der Behandlung.

7. Es wird diskutiert, daß der blutdrucksenkende Effekt der Blutvolumenverminderung durch Spironolactone infolge verschiedener Gegenregulationsmechanismen modifiziert wird.

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  1. Department Innere Medizin (Abt. Nephrologie), Medizinische Hochschule Hannover, Germany

    H. Liebau & W. v. Jarosch

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  1. H. Liebau
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  2. W. v. Jarosch
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  3. A. Show
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Herrn Prof. Dr. H. P. Wolff zum 60. Geburtstag.

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Liebau, H., v. Jarosch, W. & Show, A. Untersuchungen zur antihypertensiven Wirkung von Spironolactone. Klin Wochenschr 52, 834–841 (1974). https://doi.org/10.1007/BF01468864

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