Effect of Na+/Ca2+ exchange inhibitor, KB-R7943 on ouabain-induced arrhythmias in guinea-pigs.
1. We investigated protective effects of KB-R7943, a Na+/Ca2+ exchange (NCX) inhibitor, on ouabain-induced tonotropy and arrhythmias in isolated whole atria and ouabain-induced changes in electrocardiogram (ECG) in the guinea-pig. 2. KB-R7943 (10 and 30 microM) suppressed the tonotropic effect of ouabain, and prolonged the onset time of extra-systole induced by ouabain in isolated atria. 3. The intravenous injection of KB-R7943 (1 and 3 mg kg-1) significantly increased the doses of ouabain required to induce ventricular premature beats (VPB), ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrest (CA) in anaesthetized guinea-pigs. 4. Lidocaine (Na+channel inhibitor) and R56865 (Na+ and Ca2+ overload inhibitor) also suppressed the ouabain-induced tonotropic effect and extra-systole in isolated atria, but Hoe-694 (Na+/H+ exchange inhibitor) or diltiazem (Ca2+ channel inhibitor) did not affect them. 5. Lidocaine also increased the doses of ouabain required to induce VPB, VT, VF and CA in anaesthetized guinea-pigs. 6. From these results, we conclude that KB-R7943 suppresses ouabain-induced arrhythmias through inhibition of the reverse-mode NCX.
Watano
T
T
Department of Pharmacology, Fukushima Medical University, School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan. watano@cc.fmu.ac.jp
Harada
Y
Y
Harada
K
K
Nishimura
N
N
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D016275:Atrial Function / Q000187:drug effects*; D002316:Cardiotonic Agents; D006168:Guinea Pigs; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D010042:Ouabain; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D002316:Cardiotonic Agents; D019831:Sodium-Calcium Exchanger; D014662:Vasoconstrictor Agents; D010042:Ouabain; D008012:Lidocaine; D013890:Thiourea