Cardiovascular effects of Y-27632, a selective Rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model.
Y-27632, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate, is a selective Rho-associated kinase inhibitor, which has been suggested to possess multiple clinical applications based on the in vitro observations. Since information regarding in vivo cardiovascular effects of Y-27632 is still limited, we assessed them using the halothane-anesthetized, closed-chest canine model. Administration of Y-27632 in a dose of 0.01 mg/kg, i.v. significantly decreased total peripheral vascular resistance together with an increase of cardiac output without affecting other cardiovascular parameters. Moreover, additional administration of Y-27632 in a dose of 0.1 mg/kg, i.v. significantly decreased blood pressure and left ventricular end-diastolic pressure, increased the heart rate and cardiac contractility, enhanced atrioventricular conduction and shortened the repolarization process as well as the effective refractory period. These results indicate that Y-27632 exerts a potent arterio-venodilator action with cardiostimulatory effects possibly through the sympathetic reflex in the in vivo canine model.
Takahara
Akira
A
Department of Pharmacology, University of Yamanashi Faculty of Medicine, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan.
Sugiyama
Atsushi
A
Satoh
Yoshioki
Y
Yoneyama
Masahiko
M
Hashimoto
Keitaro
K
D000577:Amides / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects* / Q000201:enzymology; D002352:Carrier Proteins / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D054460:rho-Associated Kinases
D000577:Amides; D018685:Anesthetics, Inhalation; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C015482:protein kinase modulator; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D006221:Halothane