Jt. Barron et al., CYTOPLASMIC REDOX POTENTIAL AFFECTS ENERGETICS AND CONTRACTILE REACTIVITY OF VASCULAR SMOOTH-MUSCLE, Journal of Molecular and Cellular Cardiology, 29(8), 1997, pp. 2225-2232
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.