DIFFERENTIAL REGULATION OF GLUCOSE AND GLYCOGEN-METABOLISM IN VASCULAR SMOOTH-MUSCLE BY EXOGENOUS SUBSTRATES

The aim of this study was to determine whether the pathways of glycoly sis and glycogenolysis can be independently modulated by the provision of acetate or pyruvate as exogenous substrates. Hog carotid artery se gments were allowed to replete glycogen stores to over 6 mu mol/g of n ew C-13-labeled glycogen by incubation at 37 degrees C with 5 mM [1-C- 13]glucose for 6-16 h and then were isometrically contracted for 3 h w ith 80 mM KCl in the presence of 5 mM [2-C-13]glucose and either 2 mM sodium acetate or 5 mM sodium pyruvate. Measurements were made of tota l lactate production, glucose utilization, glycogen utilization, isome tric force, [2-C-13]lactate and [3-C-13]lactate production. Compared t o experiments with glucose as the sole exogenous substrate, provision of pyruvate significantly decreased glucose utilization (by 28%) but i nsignificantly decreased glycogen utilization. In contrast, provision of acetate resulted in a statistically insignificant decrease in gluco se utilization (by 23%) and an increase in glycogen utilization (by 20 %). The fraction of [3-C-13]pyruvate derived from glycogen that was co nverted to [3-C-13]lactate was significantly decreased in the presence of acetate despite the enhanced glycogen utilization. Despite these a lterations in cellular energy balance, isometric force generation and maintenance was similar for all experimental groups. This differential regulation of glycolysis and glycogenolysis may either reflect the co mpartmentation of these pathways or suggest a novel regulation of carb ohydrate metabolism in vivo. (C) 1997 Academic Press Limited.