Differential effects of fatty acids on glycolysis and glycogen metabolism in vascular smooth muscle.
The effects of fatty acids of different chain lengths on aerobic glycolysis, lactic acid production, glycogen metabolism and contractile function of vascular smooth muscle were investigated. Porcine carotid artery segments were treated with 50 microM iodoacetate and perchloric acid tissue extracts were then analyzed by 31P-NMR spectroscopy to observe the accumulation of phosphorylated glycolytic intermediates so that the activity of the Embden-Myerhof pathway could be tracked under various experimental paradigms. Aerobic glycolysis and lactate production in resting arteries were almost completely inhibited with 0.5 mM octanoate, partially inhibited with 0.5 mM acetate and unaffected by 0.5 mM palmitate. Inhibition of glycolysis by octanoate was not attributable to inhibition of glucose uptake or glucose phosphorylation. Basal glycogen synthesis was unchanged with palmitate and acetate, but was inhibited by 52% with octanoate incubation. The characteristic glycogenolysis which occurs upon isometric contraction with 80 mM KCl in the absence of fatty acid in the medium was not demonstrable in the presence of any of the fatty acids tested. Glycogen sparing was also demonstrable in norepinephrine contractions with octanoate and acetate, but not with palmitate. Additionally, norepinephrine-stimulated isometric contraction was associated with enhanced synthesis of glycogen amounting to 6-times the basal rate in medium containing octanoate. Contractile responses to norepinephrine were attenuated by 20% in media containing fatty acids. Thus, fatty acids significantly alter metabolism and contractility of vascular smooth muscle. Fatty acids of different chain lengths affect smooth muscle differentially; the pattern of substrate utilization during contraction depends on the contractile agonist and the fatty acid present in the medium.
Barron
J T
JT
Department of Medicine, Rush Medical College, Rush-Presbyterian St. Luke's Medical Center, Chicago 60612.
Kopp
S J
SJ
Tow
J P
JP
Parrillo
J E
JE
D000818:Animals; D002339:Carotid Arteries; D005227:Fatty Acids / Q000502:physiology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D006019:Glycolysis; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D009682:Magnetic Resonance Spectroscopy; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology; D011188:Potassium / Q000502:physiology; D013552:Swine
D005227:Fatty Acids; D007461:Iodoacetates; D006003:Glycogen; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D011188:Potassium; D019807:Iodoacetic Acid; D009638:Norepinephrine