Modulation of Na+/H+ exchange isoform 1 mRNA expression in isolated rat hearts

Na+/H+ exchange (NHE) has been demonstrated to mediate myocardial ischemia and reperfusion injury as well as injury produced by hydrogen peroxide (H2O2) or lysophosphatidylcholine (LPC). However, changes in gene expression in response to injurious factors have not been extensively studied. We examined Na+/H+ exchange isoform 1 (NHE-1) expression using Southern detection of the RT-PCR product in response to 30 min of global ischemia with or without reperfusion in isolated rat hearts or to 30 min of exposure to either H2O2 (100 mu M) or LPC (5 mu M). We also determined whether ischemic preconditioning (2 x 5-min ischemia) alters basal NHE-1 expression or the subsequent response to insult. Ischemia with or without reperfusion increased NHE-1 expression approximately sevenfold (P < 0.05), whereas either H2O2 or LPC increased expression approximately twofold. Preconditioning reduced NHE-1 message by similar to 70% (P < 0.05) and significantly attenuated the effects of ischemia, H2O2, or LPC. The internal standard, p-globin was unaffected by any treatment. Our results indicate that NHE-1 expression is rapidly increased in response to ischemia with or without reperfusion as well as in response to H2O2 Or LPC. In contrast, preconditioning was associated with downregulation of NHE-1. These results may be important in furthering our understanding of NHE-1 in cardiac disease states and suggest that the antiporter adapts rapidly to cardiac conditions associated with pathology.