Natriuretische Peptide: Physiologische, pathophysiologische und klinische Aspekte

Zusammenfassung.

Ein entscheidender Schritt für das Verständnis der Physiologie des Herz-Kreislaufsystems und der Identifizierung des Herzens als endokrines Organ gelang DeBold et al. im Jahr 1981. Er zeigte, dass die Injektion eines Extraktes aus Vorhofgewebe eine Natriurese und Blutdrucksenkung induziert. Diese Beobachtung führte zur Entdeckung einer Familie von Peptiden, die sich in ihrer biochemischen Struktur nur wenig unterscheiden und den Salz- und Wasserhaushalt des Organismus beeinflussen. Mitglieder dieser Peptidfamilie sind atriales oder A-Typ-natriuretisches Peptid (ANP), B-Typ-natriuretisches Peptid (BNP), C-Typ-natriuretisches Peptid (CNP) und Urodilatin (URO) mit unterschiedlichen Hauptsyntheseorten im Herzen (ANP, BNP), dem Gehirn (BNP), dem Gefäßendothel (CNP) und der Niere (URO). Die Erkenntnis, dass diese Peptide abgesehen von ihren Effekten auf die Herz-Kreislauf- und Nierenfunktionen auch auf das endokrine System sowie die Bronchialmuskulatur wirken, ging in den letzten Jahren mit einer intensiven Suche nach therapeutischen Anwendungsmöglichkeiten einher. So untersuchten viele Arbeitsgruppen die Wirkungen von ANP, BNP oder URO zur Behandlung des akuten Nierenversagens oder der Herzinsuffizienz. Eine Bestätigung der in einer Fülle von Experimenten beobachteten positiven Effekte durch prospektive, placebokontrollierte Studien mit hinreichend großen Patientenzahlen steht allerdings bisher noch immer aus. Abgesehen von möglichen therapeutischen Optionen könnten die Plasmaspiegel von ANP und insbesondere BNP Bedeutung als diagnostisches Kriterium für den Schweregrad und die Prognose einer Herzinsuffizienz bzw. einer Abstoßungsreaktion nach Herztransplantation erlangen.

Natriuretic Peptides: Physiological, Pathophysiological and Clinical Aspects.

A milestone was reached in cardiophysiology when in 1981 DeBold demonstrated that the heart functions as an endocrine gland by injecting an extract of atrial muscle into rats, resulting in an induction of natriuresis and a drop in blood pressure. This observation then led to the discovery of a family of related peptides with slightly different amino acid compositions working in concert to achieve the maintenance of sodium and volume homeostasis. The natriuretic peptide family consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Urodilatin (URO) with their tissue-specific distribution including the heart (ANP, BNP), brain (ANP, BNP, CNP), endothelial cells (CNP), and kidney (URO). These peptides were thought to be primarily involved in cardiovascular and renal functions but have now proven to play a role in other physiological systems. In view of their known biological effects, therapeutic efficacy from administration of ANP, BNP or URO might be anticipated, for example in acute renal failure or congestive heart failure. A number of clinical trials suggest that application of these peptides may represent a new pharmacological tool in the treatment or prevention of these diseases, but the clinical benefit still needs to be shown in large controlled studies. In addition to therapeutic options it is possible that plasma concentrations of ANP and BNP could play a role as diagnostic and prognostic markers of cardiac dysfunction.

Schlüsselwörter:

Natriuretische Peptide - akutes Nierenversagen - Herzinsuffizienz - Herztransplantation

Key words:

Natriuretic peptides - Renal failure - Congestive heart failure - Heart transplantation

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