Therapeutic potential of Na-H exchange inhibitors for the treatment of heart failure.

The Na-H exchanger (NHE) represents a family of transporters which regulate intracellular pH by removing protons in exchange for sodium influx in an electroneutral 1:1 stoichiometric relationship. Six isoforms have thus far been identified with the NHE-1 subtype representing the primary isoform in the cardiac cell. It is well-established that NHE-1 contributes to cardiac injury produced by ischaemia and reperfusion and inhibitors of the antiporter exert excellent cardioprotection. More recent evidence suggests that NHE-1 may also be important for cell growth and may contribute to the maladaptive remodelling which contributes to heart failure particularly the early hypertrophic responses. Evidence from in vitro studies suggest that NHE-1 inhibitors attenuate cardiomyocyte hypertrophy in response to various stimuli whereas in vivo studies report substantial attenuation of both hypertrophy and heart failure by these agents, especially after myocardial infarction. Accordingly, NHE-1 inhibitors could emerge as important therapeutic tools for the attenuation and treatment of heart failure.