Cardioprotection of SM-15681, an Na+/H+ exchange inhibitor in ischemic and hypoxic isolated perfused rat hearts.

Abstract

We investigated the effects of SM-15681 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide monohydrochloride) on Na+/H+ exchange activity in the myocardium and in ischemic and hypoxic injury in isolated perfused rat hearts. These effects were compared with those of ethylisopropyl amiloride (EIPA). Na+/H+ exchange activity was studied with a NH4Cl prepulse technique under HCO3(-)-free conditions. SM-15681 (10(-8)-10(-7) M) inhibited pH recovery of acidosis in the rat myocardium in a concentration-dependent manner and the IC50 value of SM-15681 (80 nM) was similar to that of EIPA. In perfused rat hearts, SM-15681 (10(-6) M) and EIPA (10(-6) M) significantly improved cardiac functions and prevented enzyme release and abnormal elevation of tissue Ca2+ content during 20 min of reperfusion after 40 min of ischemia and 20 min of reoxygenation after 30 min of hypoxia. We conclude that an Na+/H+ exchange inhibitor, SM-15681, shows cardioprotective effects on ischemia/reperfusion and hypoxia/reoxygenation injury. Our results also support the hypothesis that Na+/H+ exchange contributes to the pathophysiology of cardiac ischemic reperfusion injury.

• Authors: H Toda, T Noguchi, A Miyagishi, N Ito, K Umekawa, Y Sato, M Kitano, N Ohashi
• Journal: International journal of tissue reactions (Int J Tissue React) Vol. 21 Issue 3 Pg. 61-70 ( 1999) ISSN: 0250-0868 [Print] Switzerland
• PMID: 10645513 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Amides
• Anti-Arrhythmia Agents
• Indoles
• Neuroprotective Agents
• SM 20220
• Sodium-Hydrogen Exchangers
• Amiloride
• Hydrogen
• Sodium
• ethylisopropylamiloride

Topics

• Amides (pharmacology, therapeutic use)
• Amiloride (analogs & derivatives, pharmacology, therapeutic use)
• Animals
• Anti-Arrhythmia Agents (pharmacology, therapeutic use)
• Hydrogen (metabolism)
• Indoles (pharmacology, therapeutic use)
• Ion Transport (drug effects)
• Myocardial Ischemia (drug therapy, metabolism)
• Myocardial Reperfusion Injury (drug therapy, metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Rats, Wistar
• Sodium (metabolism)
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)