Skip to main content
main-content

01.09.2009 | Original Contribution | Ausgabe 5/2009

Basic Research in Cardiology 5/2009

Enhancement of the endothelial NO synthase attenuates experimental diastolic heart failure

Zeitschrift:
Basic Research in Cardiology > Ausgabe 5/2009
Autoren:
Dirk Westermann, Alexander Riad, Utz Richter, Sebastian Jäger, Konstantinos Savvatis, Mirjam Schuchardt, Nora Bergmann, Markus Tölle, Dirk Nagorsen, Michael Gotthardt, Heinz-Peter Schultheiss, Carsten Tschöpe

Abstract

Background

Diastolic heart failure is a rising problem with a high incidence and similar mortality and morbidity compared to patients with systolic heart failure. Nevertheless, the underlying pathophysiology is still debated.

Aim

We investigated the effect of pharmacological enhancement of endothelial nitric oxide synthase (eNOS) on experimental diastolic heart failure (DHF).

Methods

DHF was induced in 60 DAHL salt-sensitive rats by salt diet in 8-week-old animals. 30 were treated with the eNOS enhancer AVE3085 (DHFeNOS) and 30 with placebo (DHF). Rats with normal salt intake served as controls.

Results and conclusion

Diastolic dysfunction with increased diastolic stiffness constant and increased left ventricular (LV) pressure was analyzed by invasive pressure–volume loop measurements in the DHF group compared to controls. Cardiac hypertrophy as indicated by LV mass measurements by echocardiography, and increased cardiac collagen content as measured by immunohistochemistry were associated with an increased activation state of calcineurin, AKT, ERK½, but not JNK and p38 kinases. Titin isoforms were not altered in this model of DHF. Treatment with AVE3085 significantly increased eNOS mRNA and protein levels in the cardiac tissue and decreases NAD(P)H oxidase subunits p22phox and gp91phox. Diastolic dysfunction was attenuated and cardiac hypertrophy and fibrosis were improved in comparison with untreated DHF animals. This was associated with a normalized activation state of calcineurin, AKT and ERK½. Therefore, we suggest that targeting the NO system might yield a future therapeutic aim for the treatment of DHF.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de. Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

Weitere Produktempfehlungen anzeigen
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 5/2009

Basic Research in Cardiology 5/2009 Zur Ausgabe
  1. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

Neu im Fachgebiet Kardiologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Kardiologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise