Decreased urinary kallikrein activity and elevated blood pressure normalized by orally applied kallikrein in essential hypertension
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Summary
Urinary kallikrein excretion was significantly lower in patients with essential hypertension (0.48±0.05 EU/24 h) than in normotensive controls (1.26±0.14 EU/24 h). Oral administration of hog pancreatic kallikrein normalized decreased urinary kallikrein and reduced arterial pressure. The treatment-induced rise in urinary kallikrein was due to an enhanced release of endogenous enzyme, as was determined by radioimmunoassay. It is proposed that in the hypertensive patients the low urinary kallikrein excretion reflects a defect in renal kallikrein formation which is normalized by oral kallikrein. The hypotensive action of oral kallikrein as well as its stimulating effects on renal kallikrein release suggest that the kallikrein-kinin system is involved in blood pressure regulation and that impaired renal kallikrein activity may be a factor in the maintenance of essential hypertension.
Key words
Urinary kallikrein Essential hypertension Oral kallikreinNormalisierung von erniedrigter Urin-Kallikrein-Aktivität und erhöhtem Blutdruck durch orale Kallikrein-Gabe bei essentieller Hypertension
Zusammenfassung
Patienten mit essentieller Hypertension schieden signifikant weniger Kallikrein im Urin (0,48±0,05 EU/24 h) aus als normotensive Kontrollpersonen (1,26±0,14 EU/24 h). Eine 8wöchige Therapie mit oralem Schweinepankreas-Kallikrein normalisierte die verminderte Kallikreinausscheidung und führte zu einer signifikanten Blutdrucksenkung. Der durch die Behandlung induzierte Anstieg der renalen Kallikreinexkretion war Folge einer vermehrten endogenen Freisetzung des Enzyms, wie mit Hilfe eines spezifischen Radioimmunoassays festgestellt werden konnte. Es ist denkbar, daß die bei den hypertensiven Patienten nachgewiesene verminderte Kallikreinausscheidung einen Defekt in der Bildung von endogenem renalen Kallikrein reflektiert, der durch die orale Kallikrein-Therapie behoben wurde. Die blutdrucksenkende Wirkung von oralem Kallikrein sowie der stimulierende Effekt des Enzyms auf die renale Kallikreinfreisetzung lassen vermuten, daß das Kallikrein-Kinin System an der Blutdruckregulation beteiligt ist, und daß eine verminderte renale Kallikrein-Aktivität ein Faktor bei der Aufrechterhaltung der essentiellen Hypertension darstellen könnte.
Schlüsselwörter
Urin-Kallikrein Essentielle Hypertension Orale Kallikrein-TherapiePreview
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References
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