Constitutional rho-kinase regulates atrioventricular nodal conduction and ventricular repolarization of the canine heart.
Given the limited information, physiological roles of Rho-kinase in the cardiac conduction system and ventricular repolarization process were assessed in comparison with those in the coronary vascular tone. A specific Rho-kinase inhibitor Y-27632 was administered to the nutrient coronary artery of the canine isolated, blood-perfused atrioventricular node preparation under the monitoring of the ventricular monophasic action potentials. Administration of Y-27632 moderately suppressed the atrioventricular nodal conduction, slightly but significantly accelerated the repolarization process, and potently increased the coronary blood flow, whereas it hardly affected the intraventricular conduction. The estimated concentrations of Y-27632 causing the currently observed effects were enough to inhibit Rho-kinase. These results suggest that constitutional Rho-kinase functions to moderately facilitate the atrioventricular nodal conduction, slightly delay ventricular repolarization process, and significantly increase the coronary vascular tone.
Sugiyama
Atsushi
A
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho-cho, Nakakoma-gun, Yamanashi, Japan. atsushis@res.yamanashi-med.ac.jp
Takahara
Akira
A
Yatomi
Yutaka
Y
Satoh
Yoshioki
Y
Nakamura
Yuji
Y
Hashimoto
Keitaro
K
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects* / Q000502:physiology; D002036:Bundle of His / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology; D016276:Ventricular Function; D054460:rho-Associated Kinases
D000577:Amides; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases