Apelin, the Novel Endogenous Ligand of the Orphan Receptor APJ, Regulates Cardiac Contractility
ABSTRACT—The orphan receptor APJ and its recently identified endogenous ligand, apelin, exhibit high levels of mRNA expression in the heart. However, the functional importance of apelin in the cardiovascular system is not known. In isolated perfused rat hearts, infusion of apelin (0.01 to 10 nmol/L)...
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Published in: | Circulation research Vol. 91; no. 5; pp. 434 - 440 |
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Main Authors: | , , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
Hagerstown, MD
American Heart Association, Inc
06-09-2002
Lippincott Lippincott Williams & Wilkins Ovid Technologies |
Subjects: | |
Online Access: | Get full text |
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Summary: | ABSTRACT—The orphan receptor APJ and its recently identified endogenous ligand, apelin, exhibit high levels of mRNA expression in the heart. However, the functional importance of apelin in the cardiovascular system is not known. In isolated perfused rat hearts, infusion of apelin (0.01 to 10 nmol/L) induced a dose-dependent positive inotropic effect (EC5033.1±1.5 pmol/L). Moreover, preload-induced increase in dP/dtmax was significantly augmented (P <0.05) in the presence of apelin. Inhibition of phospholipase C (PLC) with U-73122 and suppression of protein kinase C (PKC) with staurosporine and GF-109203X markedly attenuated the apelin-induced inotropic effect (P <0.001). In addition, zoniporide, a selective inhibitor of Na-H exchange (NHE) isoform-1, and KB-R7943, a potent inhibitor of the reverse mode Na-Ca exchange (NCX), significantly suppressed the response to apelin (P <0.001). Perforated patch-clamp recordings showed that apelin did not modulate L-type Ca current or voltage-activated K currents in isolated adult rat ventricular myocytes. Apelin mRNA was markedly downregulated in cultured neonatal rat ventricular myocytes subjected to mechanical stretch and in vivo in two models of chronic ventricular pressure overload. The present study provides the first evidence for the physiological significance of apelin in the heart. Our results show that apelin is one of the most potent endogenous positive inotropic substances yet identified and that the inotropic response to apelin may involve activation of PLC, PKC, and sarcolemmal NHE and NCX. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0009-7330 1524-4571 |
DOI: | 10.1161/01.RES.0000033522.37861.69 |