Production of lactic acid and energy metabolism in vascular smooth muscle: effect of dichloroacetate.
Vascular smooth muscle metabolism is characterized by substantial production of lactic acid even under fully oxygenated conditions. The role the aerobic production of lactate plays in the energetics of smooth muscle is obscure and was investigated in this study. Helical strips of porcine carotid arteries were incubated in medium containing 1 mM dichloroacetate (DCA), an agent that stimulates pyruvate dehydrogenase and promotes the oxidation of glucose. Lactate production in resting muscle was decreased in the presence of DCA (0.033 +/- 0.006 vs. 0.111 +/- 0.014 mumol.g-1.min-1, P < 0.02), indicating diversion of glucose metabolism from lactate production to enhanced glucose oxidation. This was associated with reduction in the level of ATP+phosphocreatine (PCr) (0.99 +/- 0.01 vs. 1.40 +/- 0.09 mumol/g, P < 0.05) and cataplerosis of the tricarboxylic acid (TCA) cycle. Contraction by KCl was also associated with reduced lactate production in the presence of DCA (0.086 +/- 0.017 vs. 0.20 +/- 0.002 mumol.g-1.min-1, P < 0.01), but ATP+PCr normalized, and there was anaplerosis of the TCA cycle. Glycogen in control arteries declined by approximately 1.3 mumol/g over 30 min K+ contraction but was unchanged in the presence of DCA. By calculation, the glycogen spared could be accounted for by the quantity of glucose diverted from lactate production to glucose oxidation during contraction. It is concluded that the aerobic production of lactate is a mechanism affording optimal coordination and modulation of glucose supply and oxidative energy production with energy demand.
Barron
J T
JT
Department of Medicine, Rush Medical College, Chicago, Illinois 60612.
Parrillo
J E
JE
D000818:Animals; D002952:Citric Acid Cycle; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007773:Lactates / Q000096:biosynthesis*; D019344:Lactic Acid; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010710:Phosphates / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction
D007773:Lactates; D010710:Phosphates; D019344:Lactic Acid; D011189:Potassium Chloride; D006003:Glycogen; D003999:Dichloroacetic Acid; D005947:Glucose