Pattern of substrate utilization in vascular smooth muscle using C-13 isotopomer analysis of glutamate

Although vascular smooth muscle (VSM) derives the majority of its energy fr om oxidative phosphorylation, controversy exists concerning which substrate s are utilized by the tricarboxylic acid (TCA) cycle. We used C-13 isotopom er analysis of glutamate to directly measure the entry of exogenous [C-13]g lucose and acetate and unlabeled endogenous sources into the TCA cycle via acetyl-CoA. Hog carotid artery segments denuded of endothelium were superfu sed with 5 mM [1-C-13]glucose and 0-5 mM [1,2-C-13]acetate at 37 degrees C for 3-12 h. We found that both resting and contracting VSM preferentially u tilize [1,2-C-13]acetate compared with [1-C-13]glucose and unlabeled substr ates. The entry of glucose into the TCA cycle (30-60% of total entry via ac etyl-CoA) exhibited little change despite alterations in contractile state or acetate concentrations ranging from 0 to 5 mM. We conclude that glucose and nonglucose substrates are important oxidative substrates for resting an d contracting VSM. These are the first direct measurements of relative subs trate entry into the TCA cycle of VSM during activation and may provide a u seful method to measure alterations in VSM metabolism under physiological a nd pathophysiological conditions.