Na^+/H^+ Exchange Plays a Role in Hypoxia-Reoxygenation induced ICAM-1 expression in CME

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Na^+/H^+ exchange has been implicated in a mechanism for myocardial iscemia-reperfusion injury. Although cardiac myocytes have been a target for extensive resear.ch of this subject, little is known about a role of coronary microvascular endothelial cells (CMEC) in mvocardial reperfusion injury, Activation of Na^+/H^+ exchange and resultant intracellular Ca^<2+> ([Ca^<2+>]i) overload may stimulate intercellular adhesion molecule synthesis in CMEC whitch could paticipate in no reflow phenomenon. We have, therefore, investigated whether Na^+/H^+ exchange is involved in intercellular adhesion molecule-1 (ICAM-1) expression during reoxygenatlon in CMEC.The primary cultures of CMEC Isolated from adult rat hearts were subjected to simulated ischemia (hypoxic perfusion at pH6.4) for 45 minutes followed by reoxygenation at pH7.4. Dimethyl amirolide (DMA), an inhivitor of Na^+/H^+ exchanger, at a concentration of 0.1mM was added to perfusate during hypoxia and reoxygenation. The increase in [Ca^<2+>]i during hypoxia and reoxygenation was inhibited significantly (p<less than or equal>0.05) by the DMA treatment compared with the non-treatment cotrol. Northern blot analysis revealed enhanced expression of ICAM-1 m-RNA after 3 hours of reoxygenation, This was associated with immunocytochemically detected ICAM-1 protein expression which reached a maximum level at 8 hours after reoxygenation. Both ICAM-1 m-RNA and ICAM-1 protein expression were inhibited by DMA treatment. Conclusion : Na^+/H^+ exchange plays an essential role in [Ca^<2+>]i overload and ICAM-1 expression during reoxygenation in CMEC.