Cardioprotective effect of MCC-135 is associated with inhibition of Ca2+ overload in ischemic/reperfused hearts
| Autor: | Naoya Satoh, Yoshimi Kitada |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Cardiotonic Agents Ischemia chemistry.chemical_element Blood Pressure Myocardial Reperfusion Injury Calcium Pharmacology Piperazines Rats Sprague-Dawley Heart Rate Internal medicine medicine Animals Cardioprotective Agent Monensin Calcium metabolism Cardioprotection Ionophores business.industry Myocardium Benzenesulfonates food and beverages Heart medicine.disease Rats Amiloride chemistry Cardiology business Reperfusion injury Intracellular medicine.drug |
| Zdroj: | European Journal of Pharmacology. 499:179-187 |
| ISSN: | 0014-2999 |
| Popis: | Calcium (Ca2+) overload is an important pathophysiological factor in myocardial ischemic/reperfusion injury. We investigated the effects of a cardioprotective drug, MCC-135, 5-methyl-2-(1-piperazinyl) benzenesulfonic acid monohydrate, on (1) cardiac contractile dysfunction and Ca2+ overload induced by ischemia and reperfusion, and (2) the Na+/Ca2+ exchanger in Langendorff-perfused rat hearts. Low-flow 45-min ischemia and 30-min reperfusion decreased developed tension and increased ventricular Ca2+ content, effects which were ameliorated by MCC-135 and amiloride given after reperfusion. Combination of intracellular Na+ overload induced by monensin (Na+ ionophore; 5 microM) and zero-flow 15-min ischemia followed by 30-min reperfusion resulted in a decrease in developed tension and in the intracellular Na+-dependent increase in ventricular Ca2+ content. MCC-135 and the highest dose of amiloride given after reperfusion reduced the increase in ventricular Ca2+ content, whereas developed tension was increased only with MCC-135. These results suggest that the cardioprotective effect of MCC-135 in ischemia/reperfusion is associated with suppression of Ca2+ overload and is attributable to inhibition of intracellular Na+-dependent Ca2+ influx via the Na+/Ca2+ exchanger. |
| Databáze: | OpenAIRE |
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