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Angiotensin-Conversions-Enzym-Hemmung: Direkte und indirekte renale Mechanismen

Inhibition of angiotensin converting enzyme: Direct and indirect renal mechanisms

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Summary

The introduction of angiotensin-converting-enzyme (ACE)-inhibitors into the analysis of the renin-angiotensin system (RAS) had broadened our knowledge of the integral role of renin and the kidney in circulatory homeostasis and has provided a pathophysiologically based concept for the treatment of hypertension. When the RAS is activated, as it is when sodium is restricted, the renal blood supply shows the most striking vasodilatation among vascular beds assessed after ACE-inhibition. Sodium excretion rises, there is a fall in blood-pressure, and plasma concentrations of angiotensin II (AII) and aldosterone are reduced. Conversely, with sodium loading the hemodynamic and hormonal effects of ACE-inhibitors are small. In 50–60% of normal or high-renin patients with essential hypertension ACE-inhibitors induce a potentiated acute renal response: renal blood flow and sodium excretion increase more than they do in the remainder of the hypertensives or in normal subjects. The responders of the hypertensive patients fail to increase renal blood flow or to enhance renal vascular responsiveness to infused AII when they shift from a low to a high sodium intake. The altered renal response of these “sodium-sensitive” hypertensives could be related to local activity of the RAS which is insufficiently suppressed by sodium loading. ACE-inhibition reverses this failure of the renal blood supply to respond to sodium loading. Kidneys of spontaneously hypertensive rats and the renin-rich kidney of Goldblatt-hypertensive rats show an increased tubulo glomerular (TG) feedback response as compared to normal kidneys. The change in TG-feedback response might be expected to contribute to the inability of the hypertensive kidney to respond adequately to sodium loading. ACE-inhibition reduces TG-feedback sensitivity. In renal artery stenosis glomerular capillary pressure tends to be maintained by an AII mediated rise in postglomerular resistance. Suppression of AII by ACE-inhibition reduces efferent vascular tone and thus filtration rate. There is a potential for interaction of ACE-inhibitors with the kallikrein and prostaglandin pathways as well as with the sympathetic nervous system and endogenous opioids. This may modify the renal and blood pressure responses to these compounds.

Zusammenfassung

Die Einführung von Angiotensin-Conversions-Enzym(ACE)-Hemmern in die Analyse der Funktion des Renin-Angiotensin-Systems (RAS) hat die Kenntnisse über die integrale Rolle von Renin und der Niere in der Kreislaufhomöostase erweitert und ein pathophysiologisch begründetes Therapiekonzept bei arterieller Hypertension ermöglicht. Nach Aktivierung des RAS durch Natriumrestriktion steigen unter ACE-Hemmung die renale Durchblutung und die Na+-Ausscheidung an, der Blutdruck fällt ab. Die Plasma-Angiotensin II (AII)- und Aldosteronkonzentrationen sind supprimiert. Unter Na+-Beladung sind die hämodynamischen und hormonalen Effekte geringer. Bei essentieller Hypertension führen ACE-Hemmer in 50 bis 60% der normo- und hochreninämischen Patienten zu einem stärkeren Anstieg der renalen Durchblutung und der Na+-Ausscheidung sowie zu einem größeren Blutdruckabfall als bei den übrigen Hypertonikern und bei Normotensiven. Nach Na+-Beladung nimmt bei den auf ACE-Hemmer ansprechenden Hypertonikern die renale Durchblutung nicht zu, die renovaskuläre Antwort auf AII ist vermindert und der Blutdruck steigt deutlich an. Der veränderten renalen Antwort dieser „natriumsensitiven“ Hypertoniker könnte eine erhöhte intrarenale, durch Na+-Zufuhr nicht adäquat supprimierbare AII-Konzentration zugrunde liegen. Durch ACE-Hemmung wird die Störung behoben. In der Niere von spontan-hypertensiven Ratten und in der reninreichen Niere von Goldblatt-Ratten ist die tubulo-glomeruläre (TG) Feedback-Antwort des Einzelnephrons gesteigert. Diese Störung könnte an der Unfähigkeit der Hochdruckniere, Natrium adäquat auszuscheiden, beteiligt sein. ACE-Hemmung reduziert die Sensitivität des TG-Feedbacks. Bei Nierenarterienstenose wird das Filtrat aufgrund eines AII-vermittelten erhöhten Tonus des Vas efferens aufrechterhalten. AII-Suppression durch ACE-Hemmung senkt den efferenten Gefäßtonus, das Filtrat fällt. Interaktionen der ACE-Hemmer mit dem Kallikrein-Kinin- und Prostaglandinsystem sowie mit dem sympathischen Nervensystem und dem Abbau von endogenen Opioiden könnten die renale Antwort und die Blutdruckreaktion modifizieren.

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Stumpe, K.O. Angiotensin-Conversions-Enzym-Hemmung: Direkte und indirekte renale Mechanismen. Klin Wochenschr 63, 897–906 (1985). https://doi.org/10.1007/BF01738143

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