Inhibition of agonist-induced positive inotropy by a selective Rho-associated kinase inhibitor, Y-27632.
We examined the effect of Y-27632 ((+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclo-hexanecarboxamide), a selective Rho-associated kinase (ROCK) inhibitor, on agonist-induced inotropy in isolated mouse left atria. Endothelin-1, angiotensin-II, and prostaglandin F(2)(alpha) (PGF(2)(alpha)) produced positive inotropy, which was significantly attenuated by Y-27632 (100 microM). On the other hand, isoproterenol-induced positive inotropy was not attenuated by the drug. These results provide the first evidence that the Rho/ROCK pathway is involved in endothelin-1-, angiotensin-II-, and PGF(2)(alpha)-induced positive inotropy, but not in beta-adrenoceptor-mediated positive inotropy.
Nishimaru
Kazuhide
K
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Tanaka
Yoshio
Y
Tanaka
Hikaru
H
Shigenobu
Koki
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects / Q000201:enzymology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D054460:rho-Associated Kinases
D000318:Adrenergic beta-Agonists; D000577:Amides; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases