Open AccessProtective Effect of Na+/H+ Exchange Inhibitor, SM-20550, on Impaired Mitochondrial Respiratory Function and Mitochondrial Ca2+ Overload in Ischemic/Reperfused Rat Hearts
Author(s) -
Seigo Yamamoto,
Kazuki Matsui,
Naohito Ohashi
Publication year - 2002
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-200204000-00013
Subject(s) - ischemia , mitochondrion , oxidative phosphorylation , ventricular pressure , medicine , respiratory system , respiration , cardiology , anesthesia , pharmacology , endocrinology , chemistry , blood pressure , biochemistry , anatomy
The aim of this study was to investigate whether a selective Na+/H+ exchange inhibitor, SM-20550, can modulate the mitochondrial respiratory function and mitochondrial Ca2+ content in isolated rat hearts subjected to 40 min of ischemia and 20 min of reperfusion. SM-20550 (10, 100 nM) was administered for 5 min prior to ischemia and for 20 min during the reperfusion period. At 20 min after reperfusion, treatment with SM-20550 (10, 100 nM) improved the recovery of left ventricular developed pressure and suppressed the rise in left ventricular end-diastolic pressure. Mitochondrial function, assessed by the state 3 oxygen respiration rate, respiratory control index, and oxidative phosphorylation rate, was significantly impaired after ischemia/reperfusion. Administration with SM-20550 (10, 100 nM) attenuated the impaired mitochondrial function, improving the state 3 respiration rate, respiratory control index, and oxidative phosphorylation rate. The mitochondrial Ca2+ content was significantly increased after ischemia/reperfusion but was suppressed by treatment with SM-20550 (10, 100 nM). A significant linear correlation was observed between the respiratory control index and mitochondrial Ca2+ content in the ischemic/reperfused hearts. In conclusion, SM-20550 improved the postischemic recovery of left ventricular function and concurrently protected mitochondrial function mediated by preventing mitochondrial Ca2+ overload.