Effects of isoprenaline on cytosolic calcium concentrations and on tension in the porcine coronary artery.
1. Using front-surface fluorometry and fura-2-loaded medial strips of the porcine coronary artery, cytosolic Ca2+ concentration ([Ca2+]i) and tension development were simultaneously monitored in an attempt to determine the mechanisms of vasorelaxation induced by l-isoprenaline (Iso). 2. Iso actively decreased [Ca2+]i of the strips at rest, both in the presence and absence of extracellular Ca2+. 3. In the presence of extracellular Ca2+, depolarization with high-external K+ solution induced an elevation of [Ca2+]i and tension of the rapid increase and sustained, steady-state type; both levels depended on external K+ concentration. When Iso was applied at the time of steady state of high-K(+)-induced [Ca2+]i elevation, there was an initial transient reduction (the first component) followed by a subsequent sustained reduction (the second component) of [Ca2+]i. For a given [Ca2+]i level during high-K+ depolarization, the tension developed in the presence of Iso was smaller than that in its absence. Thus, the [Ca2+]i-tension relationship during the steady state of high-K(+)-induced contraction was shifted to the right by Iso. Pretreatment with ryanodine, a compound which depletes Ca2+ stored in the sarcoplasmic reticulum, abolished the first component, but not the second sustained decrease in [Ca2+]i by Iso. 4. In the presence of extracellular Ca2+ (1.25 mM), histamine (Hist) induced an abrupt (the first component) and then sustained (the second component) elevations of [Ca2+]i, while the tension rose rapidly to reach the peak, and then, gradually declined. The second, but not the first, component of [Ca2+]i elevation depended on extracellular Ca2+. Iso inhibited both the first and the second components of [Ca2+]i elevation and the contraction induced by Hist, in a concentration-dependent manner (IC50, 2 x 10(-8) M for the first component, and 5 x 10(-8) M for the second component). Cumulative application of Hist (10(-7)-10(-4) M) increased [Ca2+]i and tension with the [Ca2+]i-tension relationship shifting to the left from that observed with high K+. The [Ca2+]i-tension relationship during the Hist-induced contraction shifted to the right by Iso. In contractions induced by a higher concentration (> or = 6 x 10(-5) M) of Hist, despite the negligible decrease in [Ca2+]i, Iso could relax the muscle in a concentration-dependent manner. 5. In the absence of extracellular Ca2+, Hist induced transient elevations of [Ca2+]i and tension, possibly due to a release of Ca2+ from intracellular stores, and with similar time courses to those of the first component observed in the presence of extracellular Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)
Ushio-Fukai
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Division of Molecular Cardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abe
S
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Kobayashi
S
S
Nishimura
J
J
Kanaide
H
H
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D013552:Swine; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
D012433:Ryanodine; D002110:Caffeine; D006632:Histamine; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium