[Structure and physiological role of NHE1 and pharmacological regulation of its activity].

This article summarizes results of preclinical and clinical trials concerning the effects of NHE1 inhibitors and prospects for their clinical application. NHE1 has been identified as the most abundant isoform of Na+/H+ exchanger in the heart of mammals. NHE1 regulates pH homeostasis, cell proliferation, migration, adhesion, and apoptosis. Ischemic activation of the NHE1 in myocardium results in intracellular calcium overload, which aggravates ischemic/reperfusion injury. In accordance with results of preclinical experimental studies, selective inhibition of the sarcolemmal NHE1 can delay progression of injury during ischemia, thereby reducing myocardial necrosis and improving recovery of ventricular function upon reperfusion. Inhibitors of NHE1, which can provide beneficial effect in the clinical treatment of these conditions, are currently under preclinical and clinical tests. At present, there are 481 NHE inhibitors known according to the Thomson Reuters Integrity database.