EFFECTS OF DILTIAZEM ON FORCE, [CA2-METABOLISM IN PORCINE CORONARY-ARTERY(]I, AND ENERGY)

The effects of diltiazem, a coronary-specific calcium antagonist, on i sometric force generation and [Ca2+]i were measured in isolated porcin e coronary artery and related to measured changes in both oxidative an d aerobic glycolytic metabolism. Diltiazem, at concentrations ranging from 0.1 to 100 muM, inhibited K+ depolarization-induced increases in tension, intracellular calcium, oxygen consumption, and aerobic lactat e release. Inhibition of tension, free calcium content, and oxygen con sumption was dependent on diltiazem concentration, whereas inhibition of aerobic lactate release was not strongly dependent on diltiazem con centration. Aerobic lactate release, demonstrated to be coupled to Na-pump activity in porcine coronary artery, was inhibited by diltiazem, but ouabain-sensitive accumulation of potassium by potassium-depleted tissues was not. Diltiazem therefore appears to uncouple the relation ship between Na+-pump activity and aerobic glycolysis characteristic o f coronary artery metabolism. Depolarization-induced increases in oxyg en consumption measured in untethered preparations to reduce active te nsion were also inhibited by diltiazem at concentrations greater-than- or-equal-to 3 muM. Diltiazem therefore inhibits depolarization-induced increases in intracellular calcium and tension and has major effects on both the contractile and noncontractile components of energy metabo lism in coronary arteries.