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- W2028014641 abstract "Inhibition of Na(+)/H(+) (NHE) and Na(+)/Ca(2+) (NCE) exchangers prevents myocardial ischemia/reperfusion injury by preventing cardiomyocyte Ca(2+) overload. We hypothesized that it may influence ischemic/reperfused myocardium also indirectly by preventing endothelial Ca(2+) accumulation, and thereby by attenuating reperfusion-induced formation of nitric oxide (NO) and/or oxygen free radicals. Langendorff-perfused rat hearts were subjected to 30-min ischemia and 30-min reperfusion. Myocardial outflow of NO (nitrite+nitrate) and hydroxyl radical (*OH, salicylate method), and functional recoveries were followed during reperfusion. In all groups, there was a transient rise in NO and *OH outflow upon reperfusion. An inhibitor of NHE, cariporide (10 microM) [(4-Isopropyl-3-methylsulfonyl-benzoyl)-quanidine methanesulfonate], and an inhibitor of the reverse mode of NCE, KB-R7943 (5 microM) (2-[4-(4-Nitrobenzyloxy)phenyl]ethyl]isothiourea mesylate), decreased NO and *OH formation, reduced contracture, and improved the recovery of mechanical function during reperfusion, compared to the untreated hearts. The formation of NO was reduced by 40% by 100 microM N(G)-methyl-L-arginine acetate salt (L-NMMA, NO synthase inhibitor), and not affected by 50 microM L-NMMA. *OH formation, contracture, and the functional recoveries were affected neither by 50 nor by 100 microM L-NMMA. Also, the effects of cariporide and KB-R7943 were unaffected by 100 microM L-NMMA. This study shows for the first time that the inhibition of NHE and NCE attenuates post-ischemic myocardial formation of NO and *OH, suggesting that prevention of Ca(2+) overload is cardioprotective via these mechanisms. The results indicate, however, that NO synthase pathway did not interfere with the protection afforded by NHE or NCE in our model." @default.
- W2028014641 created "2016-06-24" @default.
- W2028014641 creator A5010991884 @default.
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- W2028014641 date "2003-02-01" @default.
- W2028014641 modified "2023-10-16" @default.
- W2028014641 title "Role of nitric oxide and free radicals in cardioprotection by blocking Na+/H+ and Na+/Ca2+ exchange in rat heart" @default.
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- W2028014641 doi "https://doi.org/10.1016/s0014-2999(03)01302-5" @default.
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