An Important Role for the Na+‐Ca2+ Exchanger in the Decrease in Cytosolic Ca2+ Concentration induced by Isoprenaline in the Porcine Coronary Artery

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Abstract
The role of the Na+‐Ca2+ exchanger (NCX) in the mechanism of the isoprenaline (Iso)‐induced vasorelaxation was investigated by simultaneously monitoring the intracellular Ca2+ concentration ([Ca2+]i) and tension of fura‐2‐loaded medial strips of porcine coronary arteries. Normal physiological salt solution (PSS) contained 137.3 mm Na+ and 5.9 mm K+. During the sustained phase of contraction, Iso induced only a transient decrease in [Ca2+]i when contraction was induced by depolarization with 118 mm K+ solution containing 25.2 mm Na+. When contraction was induced with 30 mm K+ in PSS containing 113.2 mm Na+, Iso induced a sustained decrease in [Ca2+]i, whereas in contractions induced by 30 mm K+ in a low Na+ (25.2 mm Na+) PSS, Iso transiently decreased [Ca2+]i. Replacement of Ca2+ with Ba2+ (which cannot be extruded by the Ca2+ pumps but can be extruded through the NCX) resulted in decreased [Ba2+]i induced by Iso in normal but not in low Na+ PSS. On the other hand, Iso induced a sustained decrease in [Ca2+]i when strips were pre‐contracted by U46619, a thromboxane A2 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 [Ca2+]i and tension. However, Iso‐induced sustained decreases in [Ca2+]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 [Ca2+]i and tension of the porcine coronary arterial smooth muscle.