Cardiac effects of a selective rho-associated kinase inhibitor, Y-27632, assessed in canine isolated, blood-perfused heart preparations.
Chronotropic, inotropic and coronary effects of Y-27632 ((+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride, monohydrate), a specific inhibitor of Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK), were assessed using canine isolated, blood-perfused heart preparations. Y-27632 slightly enhanced sinoatrial automaticity and significantly increased coronary blood flow, while it decreased ventricular contraction. The concentrations of Y-27632 needed to cause the currently observed changes were similar to those inhibiting ROCK in a previous in vitro study. These results suggest that the constitutional ROCK in the heart mainly regulates the ventricular contractility and coronary vascular tone rather than the sinoatrial automaticity.
Sugiyama
Atsushi
A
Department of Pharmacology, Yamanashi Medical University, Nakakoma-gun, Japan. atsushis@res.yamanashi-med.ac.jp
Yatomi
Yutaka
Y
Takahara
Akira
A
Satoh
Yoshioki
Y
Hashimoto
Keitaro
K
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003427:Cross Circulation; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases