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Decrease in plasma noradrenaline levels following long-term treatment with prindolol in patients with essential hypertension

Die Senkung der Plasma-Noradrenalin-Konzentration bei Patienten mit essentieller Hypertonie nach Langzeitbehandlung mit Prindolol

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Zusammenfassung

15 Patienten (4 Frauen, 11 Männer; 21–55 Jahre alt) mit einer leichten bis mittelschweren essentiellen Hypertonie (EH) wurden nach einer 2wöchigen Placeboperiode mit steigenden Dosen von Prindolol behandelt (15–38 mg/die im Mittel) und auf einer Erhaltungsdosis von durchschnittlich 32 mg/die insgesamt 16 Wochen lang gehalten. Blutdruck (BD), Herzfrequenz und Plasmanoradrenalin (PNA)-Konzentration wurden unter standardisierten Bedingungen (liegen, stehen, gehen) am Ende der 2-wöchigen Placeboperiode und nach der experimentellen Behandlungsperiode gemessen. Die Ergebnisse wurden mit denen einer normotensiven, unbehandelten Kontrollgruppe (NS) verglichen. Nach durchschnittlich 16 Wochen Prindololbehandlung fiel der BD von 163/113 mm Hg auf 129/91 mm Hg im Mittel ab. Die PNA-Spiegel lagen bei EH vor Prindolol signifikant höher als bei NS (liegen: 272±22.0 ng/l (mean±SEM) vs. 135±15.1 ng/l, stehen: 448±31.9 ng/l vs. 359±18.4 ng/l, gehen: 388±22.5 ng/l vs. 234±22.1 ng/l). Bei EH führte die chronische Gabe von Prindolol zu einem signifikanten Abfall der PNA-Konzentrationen unter allen drei Testbedingungen auf Spiegel, die sich nicht mehr signifikant von denen der NS unterschieden. Die adrenerge Reaktion auf die aufrechte Körperhaltung, gemessen durch den prozentualen Anstieg der PNA, war signifikant geringer bei EH vor Prindolol, verglichen mit dem prozentualen Anstieg bei NS. Unter Prindolol war die adrenerge Reaktion nicht aufgehoben, sie zeigte sogar die Tendenz, sich den Verhältnissen anzugleichen wie sie bei NS gefunden wurden. Vor Prindolol korrelierte unter basalen Bedingungen der diastolische BD eng mit der entsprechenden PNA-Konzentration (p<0.01,r=0.66,n=15). Diese Korrelation konnte nach der Prindolol-Behandlung nicht mehr aufgestellt werden. Die Abnahme von PNA nach Langzeitbehandlung mit Prindolol korrelierte nicht mit dem Abfall des BD. Die Abnahme des PNA-Spiegels spricht für eine verminderte Aktivität des sympathischen Nervensystems, die zur antihypertensiven Wirkung von Prindolol beitragen könnte.

Summary

15 patients (4 females, 11 males, 21 to 55-year old) with mild to moderate essential hypertension (EH) were treated with placebo for two weeks and thereafter with increasing doses of prindolol (15 to 38 mg/day in the mean) and kept on a mean maintenance dosage of 32 mg/day for an average of 16 weeks in all. Blood pressure (BP), heart rate und plasma noradrenaline (PNA) concentrations were measured under standardized conditions (supine, standing, walking) at the end of two weeks on placebo and after the experimental treatment period. The results were compared to those of a group of 15 normotensive untreated control subjects (NS): after an average of 16 weeks on prindolol BP fell from 163/113 mm Hg to 129/91 mm Hg in the mean. PNA levels in EH before prindolol were significantly higher than in NS (supine: 272±22.0 ng/l (mean±SEM) vs. 135±15.1 ng/l, standing: 448±31.9 ng/l vs. 359±18.4 ng/l, walking: 388±22.5 ng/l vs. 234±22.1 ng/l). In EH chronic administration of prindolol led to a significant decrease in PNA concentrations under all the three test conditions to levels which did not differ significantly any more from those derived from NS. The adrenergic response to upright posture reflected in the percentage increase in PNA was significantly less in EH before prindolol when compared to the percentage increase in NS. On prindolol the adrenergic response was not abolished, yet it tended to approach the values found in NS. Before prindolol under resting conditions diastolic BP correlated closely with the corresponding PNA levels (p<0.01,r=0.66,n=15). This correlation could not be reestablished after prindolol treatment. The decrease in PNA after long-term treatment with prindolol was not correlated to the fall in blood pressure. The decrease in PNA indicates a lower activity of the sympathetic nervous system which may contribute to the antihypertensive effect of prindolol.

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  1. Zentrum der Inneren Medizin, Abteilung für Nephrologie, Johann-Wolfgang-Goethe-Universität Frankfurt/Main, Germany

    H. M. Brecht, F. Banthien & W. Schoeppe

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Brecht, H.M., Banthien, F. & Schoeppe, W. Decrease in plasma noradrenaline levels following long-term treatment with prindolol in patients with essential hypertension. Klin Wochenschr 54, 1095–1105 (1976). https://doi.org/10.1007/BF01469113

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