An important role for the Na+-Ca2+ exchanger in the decrease in cytosolic Ca2+ concentration induced by isoprenaline in the porcine coronary artery.
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.
Yamanaka
Jun
J
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan.
Nishimura
Junji
J
Hirano
Katsuya
K
Kanaide
Hideo
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000378:metabolism; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012964:Sodium / Q000008:administration & dosage / Q000378:metabolism; D012965:Sodium Chloride; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D026902:Potassium Channel Blockers; D019831:Sodium-Calcium Exchanger; D014662:Vasoconstrictor Agents; D001464:Barium; D012965:Sodium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D012964:Sodium; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium