Objective: To determine the effects of HOE 694, a new and potent Na(+)-H+ exchanger blocker, on transient inward current (It(i)) and Na(+) - Ca(2+) exchange during hypoxia-reoxygenation in guinea pig cardiomyocytes. METHODS. Cardiomyocytes were isolated from adult guinea pig ventricle. Experiment was performed in an experimental chamber that allowed the cells to be exposed to a sufficiently low O2 pressure. The cells were subjected to hypoxia and reoxygenation. The ionic currents were studied with patch clamp technique.
Results: In the absence of HOE 694, hypoxia-reoxygenation induced It(i) in 12 of 15 experiments; but in cardiomyocytes pretreated with HOE 694 (10 approximately 50 micro mol/L), the incidence of It(i) observed during reoxygenation was reduced to 5 of 11 experiments and 3 of 10 experiments, P < 0.05 vs control respectively. The Na(+) - Ca(2+) exchange current was unaffected by HOE 694 under normoxic condition. However, when cells were pretreated with 10 micromol/L HOE 694 for 10 min, then subjected to hypoxia condition, the Na(+) - Ca(2+) exchange current significantly inhibited.
Conclusions: Blockade of the Na(+)-H+ exchange by HOE 694 could reduce Ca(2+) overload upon hypoxia-reoxygenation, and inhibition of Na(+) - H+ exchange may also indirectly decrease Na(+) - Ca(2+) exchange activity during hypoxia.