Effects of diltiazem on force, [Ca2+]i, and energy metabolism in porcine coronary artery.
The effects of diltiazem, a coronary-specific calcium antagonist, on isometric force generation and [Ca2+]i were measured in isolated porcine coronary artery and related to measured changes in both oxidative and aerobic glycolytic metabolism. Diltiazem, at concentrations ranging from 0.1 to 100 microM, inhibited K+ depolarization-induced increases in tension, intracellular calcium, oxygen consumption, and aerobic lactate release. Inhibition of tension, free calcium content, and oxygen consumption was dependent on diltiazem concentration, whereas inhibition of aerobic lactate release was not strongly dependent on diltiazem concentration. 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 relationship between Na(+)-pump activity and aerobic glycolysis characteristic of coronary artery metabolism. Depolarization-induced increases in oxygen consumption measured in untethered preparations to reduce active tension were also inhibited by diltiazem at concentrations > or = 3 microM. Diltiazem therefore inhibits depolarization-induced increases in intracellular calcium and tension and has major effects on both the contractile and noncontractile components of energy metabolism in coronary arteries.
Campbell
J D
JD
Department of Physiology and Biophysics, University of Cincinnati, Ohio.
Paul
R J
RJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine
D007773:Lactates; D019344:Lactic Acid; D011189:Potassium Chloride; D000254:Sodium-Potassium-Exchanging ATPase; D004110:Diltiazem; D002118:Calcium