An Important Role for the Na + ‐Ca 2+ Exchanger in the Decrease in Cytosolic Ca 2+ Concentration induced by Isoprenaline in the Porcine Coronary Artery

The role of the Na + ‐Ca 2+ exchanger (NCX) in the mechanism of the isoprenaline (Iso)‐induced vasorelaxation was investigated by simultaneously monitoring the intracellular Ca 2+ concentration ([Ca 2+ ] i ) and tension of fura‐2‐loaded medial strips of porcine coronary arteries. Normal physiological salt solution (PSS) contained 137.3 m m Na + and 5.9 m m K + . During the sustained phase of contraction, Iso induced only a transient decrease in [Ca 2+ ] i when contraction was induced by depolarization with 118 m m K + solution containing 25.2 m m Na + . When contraction was induced with 30 m m K + in PSS containing 113.2 m m Na + , Iso induced a sustained decrease in [Ca 2+ ] i , whereas in contractions induced by 30 m m K + in a low Na + (25.2 m m Na + ) PSS, Iso transiently decreased [Ca 2+ ] i . Replacement of Ca 2+ with Ba 2+ (which cannot be extruded by the Ca 2+ pumps but can be extruded through the NCX) resulted in decreased [Ba 2+ ] i induced by Iso in normal but not in low Na + PSS. On the other hand, Iso induced a sustained decrease in [Ca 2+ ] i when strips were pre‐contracted by U46619, a thromboxane A 2 analogue, in PSS. Various types of K + channel blockers (iberiotoxin, 4‐aminopyridine, apamin or glibenclamide) or combinations of these blockers failed to completely inhibit the Iso‐induced decreases in [Ca 2+ ] i and tension. However, Iso‐induced sustained decreases in [Ca 2+ ] i during the contraction induced by U46619 were greatly inhibited in a low Na + PSS. The Iso‐induced decrease in tension during contraction by U46619 was greatly inhibited by 2′,4′‐dichlorobenzamil, a forward‐ and reverse‐mode NCX inhibitor, but not by ouabain, a selective inhibitor of Na + ,K + ‐ATPase. These results indicate that the NCX is involved in the Iso‐induced reduction of [Ca 2+ ] i and tension of the porcine coronary arterial smooth muscle.