Enhancement of sodium-calcium exchange induces positive inotropic action and potentiates ouabain effect in rat hearts.
To study the inotropic effect of enhanced Na(+)-Ca(2+) exchange in the rat papillary muscles and isolated heart, the developed tension in the rat papillary muscles was measured and the left ventricular functions were assessed in the isolated rat heart. E-4031, a selective activator for Na(+)-Ca(2+) exchange in rats, concentration-dependently increased the developed contractile tension in the rat papillary muscles (P<0.05, n=6) and the left ventricular functions in the isolated heart; KB-R7943, a selective Na(+)-Ca(2+) exchange inhibitor, exhibited opposite effect. A combination of 0.5 micromol/L ouabain and 3.0 micromol/L E-4031 resulted in a potentiation of the developed contractile tension of the rat papillary muscles from 0.25+/-0.03 g to 0.29+/-0.04 g. The combination also enhanced the augmentation of the left ventricular functions induced by ouabain. These results indicate that E-4031 exerts a positive inotropic effect on the rat papillary muscles and isolated heart via increasing the activity of Na(+)-Ca(2+) exchange, and potentiates the positive inotropic effects of ouabain.
Zhao
Hua-Chen
HC
Departments of Physiology, Shanxi Medical University, Taiyuan, Shanxi 030001, China.
Wu
Dong-Mei
DM
Cui
Xiang-Li
XL
Wu
Bo-Wei
BW
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005260:Female; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D010210:Papillary Muscles / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000502:physiology*
D002316:Cardiotonic Agents; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D010042:Ouabain