title: Cytoplasmic redox potential affects energetics and contractile reactivity of vascular smooth muscle.
abstract: Variations in the cytoplasmic redox potential (Eh) and NADH/NAD ratio as determined by the ratio of reduced to oxidized intracellular metabolite redox couples may affect mitochondrial energetics and alter the excitability and contractile reactivity of vascular smooth muscle. To test these hypotheses, the cytoplasmic redox state was experimentally manipulated by incubating porcine carotid artery strips in various substrates. The redox potentials of the metabolite couples [lactate]/[pyruvate]i and [glycerol 3-phosphate]/[dihydroxyacetone phosphate]i varied linearly (r=0.945), indicating equilibrium between the two cytoplasmic redox systems and with cytoplasmic NADH/NAD. Incubation in physiological salt solution (PSS) containing 10 mm pyruvate ([lact]/[pyr]=0.6) increased O2 consumption approximately 45% and produced anaplerosis of the tricarboxylic acid (TCA cycle), whereas incubation with 10 mm lactate-PSS ([lact]/[pyr]i=47) was without effect. A hyperpolarizing dose of external KCl (10 mM) produced a decrease in resting tone of muscles incubated in either glucose-PSS (-0.8+/-0.8 g) or pyruvate-PSS (-2.1+/-0.8 g), but increased contraction in lactate-PSS (1.5+/-0.7 g) (n=12-18, P<0.05). The rate and magnitude of contraction with 80 mm KCl (depolarizing) was decreased in lactate-PSS (P=0.001). Slopes of KCl concentration-response curves indicated pyruvate>glucose>lactate (P<0.0001); EC50 in lactate (29. 1+/-1.0 mM) was less than that in either glucose (32.1+/-0.9 mm) or pyruvate (32.2+/-1.0 mM), P<0.03. The results are consistent with an effect of the cytoplasmic redox potential to influence the excitability of the smooth muscle and to affect mitochondrial energetics.
authors.affiliation: Department of Medicine, Rush Medical College, Rush-Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Barron
authors.forename: L
authors.initials: L
authors.lastname: Gu
authors.forename: J E
authors.initials: JE
authors.lastname: Parrillo
mesh_terms: D000332:Aerobiosis; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002210:Caprylates / Q000494:pharmacology; D002339:Carotid Arteries; D002952:Citric Acid Cycle; D003593:Cytoplasm / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000502:physiology; D007773:Lactates / Q000494:pharmacology; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D019289:Pyruvic Acid / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D002210:Caprylates; D007773:Lactates; D009243:NAD; D011189:Potassium Chloride; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005947:Glucose; D002118:Calcium