Effects of the HOE 694 on transient inward current and Na(+) - Ca(2+) exchange in guinea pig cardiomyocytes.
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.
Liu
H
H
Shanghai Institute of Cardiovascular Diseases, Zhong Shan Hospital of Shanghai Medical University, Shanghai 200032.
Chen
H
H
Yang
X
X
Cheng
J
J
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D032383:Myocytes, Cardiac / Q000187:drug effects*; D019831:Sodium-Calcium Exchanger / Q000187:drug effects*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology*
D006146:Guanidines; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C074107:3-methylsulfonyl-4-piperidinobenzoyl guanidine