The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
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) induced a dose-dependent positive inotropic effect (EC 50 : 33.1±1.5 pmol/L). Moreover, preload-induced increase in dP/dt max 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 2+ exchange (NCX), significantly suppressed the response to apelin ( P <0.001). Perforated patch-clamp recordings showed that apelin did not modulate L-type Ca 2+ 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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Cites
Protein kinase C and lipid signaling for sustained cellular responses
Nishizuka, Y. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.7.7737456 · Cited by 2,499
Cited by
Apelin, a Newly Identified Adipokine Up-Regulated by Insulin and Obesity
Boucher, J., Masri, B., Daviaud, D., Gesta, S., Guigné, C., Mazzucotelli, A., Castan-Laurell, I., Tack, I., Knibiehler, B., Carpéné, C., et al. (2005) · Endocrinology · doi:10.1210/en.2004-1427 · Cited by 910
van Kimmenade, R. R., Januzzi, J. L., Ellinor, P. T., Sharma, U. C., Bakker, J. A., Low, A. F., Martinez, A., Crijns, H. J., MacRae, C. A., Menheere, P. P., et al. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.03.061 · Cited by 567
Maguire, J. J., Kleinz, M. J., Pitkin, S. L., & Davenport, A. P. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.134619 · Cited by 323
G-Protein–Coupled Receptors in Heart Disease
Wang, J., Gareri, C., & Rockman, H. A. (2018) · Circulation Research · doi:10.1161/circresaha.118.311403 · Cited by 303
Kidoya, H., Ueno, M., Yamada, Y., Mochizuki, N., Nakata, M., Yano, T., Fujii, R., & Takakura, N. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601982 · Cited by 265
Metadata
- Authors
- Szokodi, I., Tavi, P., Földes, G., Voutilainen-Myllylä, S., Ilves, M., Tokola, H., Pikkarainen, S., Piuhola, J., Rysä, J., Tóth, M., & Ruskoaho, H.
- Venue
- Circulation Research
- Published
- 2002-09-06
- Volume
- 91
- Issue
- 5
- Pages
- 434-440
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2152479803
- Cited by
- 625
- References
- 1
- FWCI
- 9.13
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Apelin, the Novel Endogenous Ligand of the Orphan Receptor APJ, Regulates Cardiac Contractility. https://app.cochat.ai/papers/10.1161/01.res.0000033522.37861.69
- The paper
- Szokodi, I., Tavi, P., Földes, G., Voutilainen-Myllylä, S., Ilves, M., Tokola, H., Pikkarainen, S., Piuhola, J., Rysä, J., Tóth, M., & Ruskoaho, H. (2002). Apelin, the Novel Endogenous Ligand of the Orphan Receptor APJ, Regulates Cardiac Contractility. Circulation Research. https://doi.org/10.1161/01.res.0000033522.37861.69
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
