Klinische Wochenschrift

, Volume 59, Issue 20, pp 1139–1147 | Cite as

Zur Rolle der Prostaglandine bei der Reninfreisetzung

  • J. C. Frölich
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Zusammenfassung

Eine Rolle der renalen Prostaglandine bei der Reninregulation wurde im Verlauf der letzten Jahre erkannt und für den Menschen partiell definiert. Infusion von Prostanoiden (Prostaglandin E2 and Prostacyclin) führt zu einer Steigerung der Reninabgabe, während Substanzen, die die Prostaglandinsynthese hemmen (Indometazin, Diclofenac) die Reninfreisetzung reduzieren. Die Interpretation der beim Menschen beobachteten Verminderung der Plasmareninaktivität durch Indometacin ist dadurch kompliziert, daß Indometacin eine Natriumretention bewirkt. Wird diese Natriumretention durch Verabfolgung einer natriumverarmten Diät verhindert, so senkt Indometacin die Reninwerte nicht mehr. Eine Erklärung für dieses Phänomen ergibt sich aus Untersuchungen an natriumverarmten Normalprobanden, bei denen zusätzlich zu Indometacin der Betablocker Propranolol verabfolgt wurde. Propranolol wurde gegeben, um die Wirkung des durch Natriumverarmung gesteigerten Sympathikotonus auf die Reninabgabe zu blockieren. Unter diesen Bedingungen bewirkte die Hemmung der Prostaglandinsynthese eine Verminderung der Plasmareninaktivität um 70%, ohne daß es zu einer Natriumretention kam. Damit wird deutlich, daß den Prostaglandinen bei der Reninregulation des Menschen eine quantitativ bedeutsame Rolle zukommt, die auch unabhängig von Veränderungen im Natriumhaushalt nachweisbar ist.

Untersuchungen zur Frage, welches der zahlreichen renalen Prostaglandine bei der Reninregulation eine Rolle spielt, zeigen, daß der Prostaglandin-Vorläufer Arachidonsäure und das Zwischenprodukt, Prostaglandin-Endoperoxid, nicht jedoch PGE2 die Reninabgabe in vitro erhöhen. Die Suche nach einem weiteren Metaboliten der Arachidonsäure im Nierenkortex führte uns zum Prostacyclin, welches sich in vivo und in vitro als hochwirksam und mit Isoproterenol äquieffektiv stimulierend auf die Reninfreisetzung erweist. Diese Befunde bilden die Grundlage für eine Hypothese, wonach Prostacyclin bei der Reninabgabe eine wesentliche Rolle spielt.

Schlüsselwörter

Renin Prostazyklin Na+-Ausscheidung Katecholamine 

Role of prostaglandins in the regulation of renin

Summary

A number of recent investigations carried out in animals, in man and in vitro have shown an important role for prostaglandins in renin release. Infusion of prostaglandins E2 and I2 can increase and blockers of prostaglandin synthesis (indomethacin, diclofenac) can block basal and diuretic enhanced renin release. Investigations in man have shown that indomethacin causes a reduction in plasma renin activity (PRA) and sodium retention. When sodium retention by indomethacin was inhibited by sodium depletion (10 mEq Na+-diet), there was no effect of indomethacin on PRA even though there was inhibition of prostaglandin biosynthesis. Because sodium depletion leads to enhanced sympathetic activity, investigations were carried out in sodium depleted volunteers in whom the effect of enhanced sympathetic activity on renin release was blocked by betareceptor blockade. Under these conditions indomethacin lowered supine and upright PRA by more then 70% even though it did not cause sodium retention. This finding suggested that β-receptor stimulated renin release in man is independent of prostaglandin synthesis. Subsequent studies showing that infusion of isoproterenol in sodium depleted normal volunteers is not affected by indomethacin provided convincing support for this concept.

The question which of the several renal prostaglandins could play a role in renin release was studied in in vitro experiments. It was shown that the prostaglandin precursor arachidonic acid and the unstable endoperoxide but not PGE2 can increase renin release. The search for an additional metabolite of arachidonic acid led to the discovery of prostacyclin synthesis in the renal cortex. PGI2 proved to be highly active in causing renin release in vivo and in vitro with an effectiveness paralleled only by isoproterenol. These studies led us to suggest that prostacyclin is the prostanoid responsible for cyclooxygenase dependent renin release.

Key words

Renin Prostacyclin Na+-Excretion Catecholamines 

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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • J. C. Frölich
    • 1
  1. 1.Fischer-Bosch-Institut für Klinische PharmakologieStuttgart

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