Na+/H+ exchanger inhibition at the onset of reperfusion decreases myocardial infarct size: role of reactive oxygen species

Phosphodiesterase 5A Inhibition Induces Na + /H + Exchanger Blockade and Protection Against Myocardial Infarction

“…1,25,26 Therefore, we hypothesized that NHE-1 inhibition by PDE5A inhibitors should also protect the heart in a similar way to that described for NHE-1 inhibition by other compounds. 3,5 Thus, we decided to explore whether the protection described for NHE-1 inhibitors when treatment started after coronary occlusion 5 would be mimicked by chronic SIL treatment.…”

Differential roles of p38-MAPK and JNKs in mediating early protection or apoptosis in the hyperthermic perfused amphibian heart

“…Accordingly, by using cariporide (HOE642), we found the NHE1, a primary pH regulatory effector (Aronson, 1985), to participate in the signaling network transducing the particular hyperthermic stimulus. NHE1 function consists of proton extrusion triggered by the transmembrane sodium gradient but has also been reported to limit ROS-induced damage in the cardiac muscle (Teshima et al, 2003;Fantinelli et al, 2006). As far as activation of JNKs is concerned, fluctuations in intracellular ion dynamics and the formation of ROS was shown to affect it at an early stage with the activity of the transmembrane Na + /K + -ATPase initially recruited, while as a late response, it was the activity of the sarcolemmal NHE1 pump that appeared to cross-talk with the JNKs pathway, exchanging intracellular H + with Na + (Figs6 and 7, respectively).…”

Redox signaling triggers protection during the reperfusion rather than the ischemic phase of preconditioning

“…Despite the fact that ROS act as second messengers in normal cells at low concentrations, at high concentrations ROS are toxic and can induce cell damage. It is well known that a burst of ROS occurs when molecular oxygen is returned to cells that have endured prolonged ischemia [2,7]. ROS are also generated during ischemia.…”