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Effects of diltiazem on calcium concentrations in the cytosol and on force of contractions in porcine coronary arterial strips
Author(s) -
Hirano Katsuya,
Kanaide Hideo,
Abe Shimako,
Nakamura Motoomi
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12700.x
Subject(s) - diltiazem , extracellular , histamine , chemistry , contraction (grammar) , calcium , biophysics , cytosol , muscle contraction , medicine , endocrinology , biochemistry , biology , enzyme , organic chemistry
1 Using front‐surface fluorometry with fura‐2‐loaded porcine coronary arterial strips, we simultaneously measured effects of a Ca 2+ antagonist, diltiazem, on cytosolic Ca 2+ concentrations ([Ca 2+ ] i ) and on tension development. 2 In the presence of extracellular Ca 2+ (1.25 m m ), histamine concentration‐dependently induced abrupt (the first component) and then sustained (the second component) elevations of [Ca 2+ ] i . In the absence of extracellular Ca 2+ , histamine induced transient elevations of [Ca 2+ ] i , and the time course was similar to that of the first component observed in the presence of extracellular Ca 2+ . Histamine caused a greater contraction for a given change in [Ca 2+ ] i than did potassium, at [Ca 2+ ] i over 300 n m . 3 Diltiazem, 10 −8 m to 10 −5 m , concentration‐dependently inhibited the second component of [Ca 2+ ] i elevation and tension development induced by histamine (10 −5 m ). Only at higher concentrations (over 10 −5 m ) did diltiazem inhibit the first component of increases in [Ca 2+ ] i and tension development induced by histamine, both in the presence and absence of extracellular Ca 2+ . 4 Diltiazem (10 −6 m ) inhibited increases in [Ca 2+ ] i and tension development induced by cumulative applications of extracellular Ca 2+ during K + ‐depolarization. The curve of [Ca 2+ ] i against tension of these Ca 2+ ‐induced contractions obtained in diltiazem‐treated strips overlapped with that obtained in untreated strips. This suggests that diltiazem has no direct effects on contractile elements. 5 In contrast, the histamine‐induced Ca 2+ ‐tension curve (second component) was shifted in parallel to the left by diltiazem. 6 We conclude that diltiazem, at therapeutic concentrations, specifically inhibits extracellular Ca 2+ ‐dependent increases in [Ca 2+ ] i , with no effects on the release of Ca 2+ from intracellular store sites or on Ca 2+ ‐sensitivity of the contractile elements involved in the contractions induced by elevations of [Ca 2+ ] i .