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Differential inhibition by the Rho kinase inhibitor Y-27632 of the increases in contractility and Ca2+ transients induced by endothelin-1 in rabbit ventricular myocytes

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Abstract

The role of Rho kinase activation in the regulation of cardiac contractility and Ca2+ signaling remains unclear, whereas its role in smooth muscle regulation has been well documented. To study the potential role of Rho kinase in the regulation of cardiac contractility and Ca2+ transients induced by endothelin-1 (ET-1) and isoproterenol, we used the Rho kinase inhibitor Y-27632 in rabbit ventricular myocardium and myocytes loaded with indo-1/AM. Y-27632 (3–30 μM) inhibited significantly the baseline contractility and Ca2+ transients. Furthermore, Y-27632 suppressed the increase in contractility and Ca2+ transients induced by ET-1 in a concentration-dependent manner, when it was used in a concentration at which it did not affect the effects of isoproterenol via β-adrenoceptors. In the presence of Y-27632, ET-1 increased cell shortening in the absence of an increase in Ca2+ transients. This is an indication that the increase in myofilament Ca2+ sensitivity induced by ET-1 is less susceptible to the inhibitory action of Y-27632. These findings imply that the Rho kinase activation may partially contribute to the ET-1-induced regulation of contractility, primarily due to an ET-1-induced increase in Ca2+ transients in rabbit ventricular myocardium.

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Acknowledgements

This work was supported in part by a Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

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  1. Li Chu

    Present address: Department of Pharmacology, Hebei Medical University, Shijiazhuang, 050051, People’s Republic of China

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  1. Department of Cardiovascular Pharmacology, Yamagata University School of Medicine , Yamagata, 990-9585, Japan

    Li Chu, Ikuo Norota & Masao Endoh

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Correspondence to Masao Endoh.

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Chu, L., Norota, I. & Endoh, M. Differential inhibition by the Rho kinase inhibitor Y-27632 of the increases in contractility and Ca2+ transients induced by endothelin-1 in rabbit ventricular myocytes. Naunyn-Schmiedeberg's Arch Pharmacol 371, 185–194 (2005). https://doi.org/10.1007/s00210-005-1032-z

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