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Cardioprotective effect of MCC-135 is associated with inhibition of Ca2+ overload in ischemic/reperfused hearts.

Abstract
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.
AuthorsNaoya Satoh, Yoshimi Kitada
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 499 Issue 1-2 Pg. 179-87 (Sep 19 2004) ISSN: 0014-2999 [Print] Netherlands
PMID15363965 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Benzenesulfonates
  • Cardiotonic Agents
  • Ionophores
  • MCC 135
  • Piperazines
  • Monensin
  • Calcium
Topics
  • Animals
  • Benzenesulfonates (pharmacology)
  • Blood Pressure (drug effects)
  • Calcium (metabolism)
  • Cardiotonic Agents (pharmacology)
  • Heart (drug effects, physiopathology)
  • Heart Rate (drug effects)
  • Ionophores (pharmacology)
  • Male
  • Monensin (pharmacology)
  • Myocardial Reperfusion Injury (physiopathology)
  • Myocardium (metabolism, pathology)
  • Piperazines (pharmacology)
  • Rats
  • Rats, Sprague-Dawley

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