Vascular control of resting metabolism in muscle

Vascular Control of Resting Metabolism in Muscle Whilst it is generally accepted that the metabolic rate of muscle will determine its own blood flow by autoregulation the reverse relationship of blood flow controlling metabolism is less understood. Investigations by Clark and colleagues (Clark et al. 1995) suggest the existence of two different vascular systems in the perfused rat hindlimb. One of these systems appears to be nutritive for muscle while the other system appears to behave as a functional shunt. When flow is selectively directed through either of these systems by vasoconstrictors or vasodilators profound metabolic changes are observed. One set of vasoconstrictors, Type A, can double the resting metabolic rate of the perfused hindlimb while the other set, Type B, can halve the resting metabolic rate of the perfused hindlimb. The aim of the present thesis was to obtain further evidence for two discretely different vascular systems in muscle and to investigate the histological nature of these two different vascular systems .. A secondary aim of the thesis was to assess the control of selective vascular recruitment over key metabolic pathways such as lactate metabolism and glycolysis, glycerol metabolism lipolysis and respiration. The first group of experiments provided further evidence for two different vascular systems in the hindlimb. One of these experiments used fluorescent microspheres to measure blood flow distribution between muscle groups and methyl-xanthine (an indicator of vascular recruitment) to assess the degree of nutritive flow. Another set of experiments provided fluorescent dye-tracing evidence for vessels supplying septa and tendons being non-nutritive conduits for the Type B response. Investigations into vasoconstrictor and flow-rate control of lactate uptake and release by muscle showed that both Type A norepinephrine (ie., concentrations of norepinephrine below I µM) and increased-flow, stimulated lactate release from the perfused hindlimb. However, when 10 mM lactate was added to the perfusion medium to stimulate lactate uptake increased flow was found to increase uptake while Type A norepinephrine decreased lactate uptake. These data indicate a mechanistic difference between flow and vasoconstrictor-stimulated metabolism. Glycerol release from the hindlimb was also regulated by vasoconstrictors suggesting a vascular control of lipid metabolism. However, no concurrent decrease in respiratory quotient or increase in fatty acid release was found during Type A stimulation, thus suggesting a vascular control of the fatty acid reesterification cycle.