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- Title
Signaling mechanisms mediating the positive inotropic response to apelin in the intact rat heart.
- Authors
Ezer, Péter; Perjés, Ábel; Skoumal, Réka; Simon, Mihály; Cziráki, Attila; Koller, Akos; Kónyi, Attila; Gábor Horváth, Iván; Ruskoaho, Heikki; Szokodi, István
- Abstract
Background: Apelin is emerging as an important regulator of the cardiovascular system. We previously demonstrated that apelin is one of the most potent endogenous stimulators of myocardial contractility; however, the signal transduction pathways mediating this effect are still obscure. Here we studied the role of protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2) in the positive inotropic effect of apelin. Methods and Results: In isolated perfused rat hearts, infusion of apelin (2 nmol/L for 20 min) induced a slowly developing and sustained increase in cardiac contractility. The improvement of cardiac function was accompanied by the activation of PKC and ERK1/2. Apelin induced a transient increase in the translocation of PKC[epsilon], but not PKC[alpha], from the cytosol to the particulate fraction, and a sustained increase in the phosphorylation of ERK1/2 in the left ventricle. Pharmacological inhibition of ERK1/2 activation significantly attenuated the inotropic response to apelin. Although inhibition of PKC reduced the inotropic effect of apelin, it did not prevent the activation of ERK1/2. Conclusions: Stimulation of apelin receptors enhances myocardial contractility via parallel and independent activation of PKC[epsilon] and ERK1/2 in the intact adult rat heart. Selective activation of PKC[epsilon] and ERK1/2 signaling may represent a novel means to support cardiac function in diseased conditions.
- Subjects
APELIN; CARDIOTONIC agents; CARDIOVASCULAR system; CARDIAC contraction; CELLULAR signal transduction
- Publication
Cardiologia Croatica, 2014, Vol 9, Issue 5/6, p244
- ISSN
1848-543X
- Publication type
Article
- DOI
10.15836/ccar.2014.244