Effect of Na+/Ca2+exchange inhibitor, KB-R7943 on ouabain-induced arrhythmias in guinea-pigs
| Autor: | Yoshimitsu Harada, Noriyasu Nishimura, Kengo Harada, Tomokazu Watano |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Pharmacology
medicine.medical_specialty Lidocaine Sodium-calcium exchanger Chemistry medicine.medical_treatment Antiarrhythmic agent Ventricular tachycardia medicine.disease Ouabain Guinea pig Endocrinology Internal medicine Ventricular fibrillation cardiovascular system medicine Diltiazem medicine.drug |
| Zdroj: | British Journal of Pharmacology. 127:1846-1850 |
| ISSN: | 0007-1188 |
| DOI: | 10.1038/sj.bjp.0702740 |
| Popis: | 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. KB-R7943 (10 and 30 μM) suppressed the tonotropic effect of ouabain, and prolonged the onset time of extra-systole induced by ouabain in isolated atria. 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. 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. Lidocaine also increased the doses of ouabain required to induce VPB, VT, VF and CA in anaesthetized guinea-pigs. From these results, we conclude that KB-R7943 suppresses ouabain-induced arrhythmias through inhibition of the reverse-mode NCX. British Journal of Pharmacology (1999) 127, 1846–1850; doi:10.1038/sj.bjp.0702740 |
| Databáze: | OpenAIRE |
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