The role of glycogen as an oxidative substrate for vascular smooth muscle (
VSM) remains controversial. To elucidate the importance of glycogen as an o
xidative substrate and the influence of glycogen flux on VSM substrate sele
ction, we systematically altered glycogen levels and measured metabolism of
glucose, acetate, and glycogen. Hog carotid arteries with glycogen content
s ranging from 1 to 11 mu mol/g were isometrically contracted in physiologi
cal salt solution containing 5 mM [1-C-13] glucose and 1 mM [1,2-C-13] acet
ate at 37 degrees C for 6 h. [1-C-13] glucose, [1,2-C-13] acetate, and glyc
ogen oxidation were simultaneously measured with the use of a C-13-labeled
isotopomer analysis of glutamate. Although oxidation of glycogen increased
with the glycogen content of the tissue, glycogen oxidation contributed onl
y similar to 10% of the substrate oxidized by VSM. Whereas [1-C-13] glucose
flux, [3-C-13] lactate production from [1-C-13] glucose, and [1,2-C-13] ac
etate oxidation were not regulated by glycogen content, [1-C-13] glucose ox
idation was significantly affected by the glycogen content of VSM. However,
[1-C-13] glucose remained the primary (similar to 40-50%) contributor to s
ubstrate oxidation. Therefore, we conclude that glucose is the predominate
substrate oxidized by VSM, and glycogen oxidation contributes minimally to
substrate oxidation.