| Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | Naunyn-Schmiedeberg's Archives of Pharmacology | ||||
| Verlag: | SPRINGER | ||||
| Ort der Veröffentlichung: | NEW YORK | ||||
| Band: | 385 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 11 | ||||
| Seitenbereich: | S. 1117-1125 | ||||
| Datum: | 2012 | ||||
| Institutionen: | Medizin > Lehrstuhl für Innere Medizin II Biologie und Vorklinische Medizin > Institut für Physiologie Biologie und Vorklinische Medizin > Institut für Physiologie > Prof. Dr. Frank Schweda | ||||
| Identifikationsnummer: |
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| Stichwörter / Keywords: | LEFT-VENTRICULAR DYSFUNCTION; BRAIN NATRIURETIC PEPTIDE; BLOOD-PRESSURE CONTROL; VASOPEPTIDASE INHIBITOR; DOUBLE-BLIND; DIFFERENTIAL EXPRESSION; CONVERTING ENZYME; RATS; OMAPATRILAT; ATRIAL; Congestive heart failure; RAS; Pharmacotherapy | ||||
| Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 63247 |
Web of ScienceZusammenfassung
Vasopeptidase inhibition (VPI), a therapeutic strategy by dual inhibition of both ACE and neutral endopeptidase 24.11, has not shown a prognostic benefit over ACE inhibition in chronic severe heart failure (CHF). Nevertheless, the effects of early treatment by VPI on cardiac remodelling have not been well assessed. We analysed the effects of early chronic VPI (50 mg/kg/day Omapatrilat) on cardiac ...
Zusammenfassung
Vasopeptidase inhibition (VPI), a therapeutic strategy by dual inhibition of both ACE and neutral endopeptidase 24.11, has not shown a prognostic benefit over ACE inhibition in chronic severe heart failure (CHF). Nevertheless, the effects of early treatment by VPI on cardiac remodelling have not been well assessed. We analysed the effects of early chronic VPI (50 mg/kg/day Omapatrilat) on cardiac remodelling and neurohumoral function during the progression of rapid ventricular pacing-induced heart failure in rabbits (early left ventricular dysfunction [ELVD]: 10 days at 330 bpm, CHF: further 10 days at 360 bpm). VPI-treated animals (ELVD-VPI n = 6; CHF-VPI n = 8) and placebo treated animals (ELVD n = 6; CHF n = 7) were compared with control rabbits (CTRL n = 5). LV fractional shortening (FS) and enddiastolic diameter (LVEDD) were assessed by echocardiography (12 MHz probe). LV BNP- and LV IL-6 gene expression was analysed quantitatively by real time PCR. Neurohumoral function was assessed by ANP, cGMP, plasma renin activity (PRA) and Aldosterone. In ELVD, LVEDD and atrial mass were significantly increased (both p < 0.05). This increase was markedly attenuated by VPI (both p < 0.05 vs. placebo). CHF was associated with a further increase in atrial mass and an increase in LV mass (both p < 0.05), which was again attenuated by VPI (atrial mass, p < 0.05 vs. untreated). LV BNP mRNA was significantly increased in CHF (p < 0.05 vs. control), and chronic VPI completely abolished this increase in ELVD and significantly attenuated it in CHF (p < 0.05 vs. CHF-placebo). Beyond that, the increase of cGMP was augmented by chronic VPI (p < 0.05 vs. placebo in CHF) in heart failure and that of Aldosterone was attenuated (p < 0.05 vs. placebo in ELVD), whereas PRA was temporarily increased (p < 0.05 vs. placebo in ELVD). Combined inhibition of ACE and NEP by VPI significantly inhibits early cardiac remodelling and LV BNP gene expression. If initiated early enough, it may slow down cardiac remodelling and represents a promising therapeutic strategy in progressive heart failure.
Metadaten zuletzt geändert: 19 Dez 2024 09:34
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