The effect of an Na+/H+ exchange inhibitor, SM-20550, on ischemia/reperfusion-induced endothelial dysfunction in isolated perfused rat hearts.

Abstract

The aim of this study was to test the protective effect of an Na+/H+ exchange (NHE) inhibitor, SM-20550, on ischemia/reperfusion-induced endothelial dysfunction. Isolated rat hearts were subjected to 30 min of global ischemia followed by 20 min of reperfusion and their responses to the endothelial-dependent vasodilator, acetylcholine, and the endothelial-independent vasodilator, nitroglycerin, before and after ischemia were examined. Acetylcholine-induced relaxation was impaired after ischemia/reperfusion while nitroglycerin induced relaxation was not. Administration of 1-10 nmol/l SM-20550 [N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid] before and after ischemia prevented impairment of acetylcholine-induced relaxation. To further understand the mechanism of SM-20550 in protecting endothelial function, we measured the inhibitory activity of SM-20550 on NHE in cultured endothelial cells. SM-20550 (1-100 nmol/l) inhibited recovery from acidosis induced by an NH4Cl prepulse in a concentration-dependent manner. Oxygen radicals from endothelial cells and leukocytes are one of the major sources of endothelial cell injury during ischemia and reperfusion. Consequently, we tested the effect of SM-20550 on H2O2-induced endothelial cell injury. SM-20550 (100-1,000 nmol/l) prevented H2O2-induced cell injury measured by lactate dehydrogenase assay. In conclusion, SM-20550 inhibited NHE in endothelial cells, protected ischemia/reperfusion-induced endothelial dysfunction and prevented H2O2-induced endothelial cell injury at higher concentrations.

• Authors: S Yamamoto, K Matsui, N Itoh, N Ohashi
• Journal: International journal of tissue reactions (Int J Tissue React) Vol. 23 Issue 1 Pg. 1-7 ( 2001) ISSN: 0250-0868 [Print] Switzerland
• PMID: 11392059 (Publication Type: Journal Article)

Chemical References

• Amidines
• Indoles
• SM 20550
• Sodium-Hydrogen Exchangers
• Hydrogen Peroxide

Topics

• Amidines (pharmacology)
• Animals
• Cattle
• Cells, Cultured
• Endothelium, Vascular (cytology)
• Heart (drug effects, physiopathology)
• Hydrogen Peroxide (pharmacology)
• Indoles (pharmacology)
• Male
• Muscle Relaxation (drug effects)
• Myocardial Ischemia (physiopathology)
• Myocardial Reperfusion (adverse effects)
• Myocardial Reperfusion Injury (physiopathology, prevention & control)
• Organ Culture Techniques
• Rats
• Rats, Sprague-Dawley
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)