CYTOPLASMIC REDOX POTENTIAL AFFECTS ENERGETICS AND CONTRACTILE REACTIVITY OF VASCULAR SMOOTH-MUSCLE

Variations in the cytoplasmic redox potential (E-h) and NADH/NAD ratio as determined by the ratio of reduced to oxidized intracellular metab olite 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 sub strates. The redox potentials of the metabolite couples [lactate]/[pyr uvate](i) and [glycerol 3-phosphate]/[dihydroxyacetone phosphate](i) v aried linearly (r=0.945), indicating equilibrium between the two cytop lasmic redox systems and with cytoplasmic NADH/NAD. Incubation in phys iological salt solution (PSS) containing 10 mM pyruvate ([lact]/[pyr]= 0.6) increased O-2 consumption similar to 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 m uscles 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 KC l (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 g lucose (32.1+/-0.9 mM) or pyruvate (32.2+/-1.0 mM), P<0.03. The result s are consistent with an effect of the cytoplasmic redox potential to influence the excitability of the smooth muscle and to affect mitochon drial energetics. (C) 1997 Academic Press Limited.