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.
The role of Rho kinase activation in the regulation of cardiac contractility and Ca(2+) 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 Ca(2+) 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 microM) inhibited significantly the baseline contractility and Ca(2+) transients. Furthermore, Y-27632 suppressed the increase in contractility and Ca(2+) 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 beta-adrenoceptors. In the presence of Y-27632, ET-1 increased cell shortening in the absence of an increase in Ca(2+) transients. This is an indication that the increase in myofilament Ca(2+) 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 Ca(2+) transients in rabbit ventricular myocardium.
Chu
Li
L
Department of Cardiovascular Pharmacology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
Norota
Ikuo
I
Endoh
Masao
M
D000318:Adrenergic beta-Agonists; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D007545:Isoproterenol; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D054460:rho-Associated Kinases
D000318:Adrenergic beta-Agonists; D000577:Amides; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C059587:Indo-1 pentaacetoxymethyl ester; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D007545:Isoproterenol; D002118:Calcium