Important differences exist between perfused and incubated (or perifused) skeletal muscle preparations with regard to their metabolism and control. A growing body of evidence suggests that the differences may be due to the role played by the vascular system. In the constant-flow perfused rat hindlimb preparation, a group of vasoconstrictors has been identified that enhance muscle metabolism and aerobic contractility. Another group of vasoconstrictors decrease muscle metabolism and aerobic contractility even though perfusate flow remains constant. All effects of both groups of vasoconstrictors are opposed by vasodilators. Because none of the vasoconstrictor effects is evident when isolated muscles are incubated or perifused, involvement of an active vascular system is indicated. Although some hormones may act directly on muscle by purely endocrine effects, a vascular component of their actions is now emerging. Mechanisms to account for vascular control of perfused skeletal muscle metabolism may involve 1) functional vascular shunts where the proportion of flow processed by these is regulated by site-specific vasomodulators, 2) a direct response to a change in the rate of supply of nutrients and removal of products, and 3) a signal substance released by vascular tissue in association with vasoconstriction that interacts with surrounding skeletal muscle cells. Impaired control at the level of the vascular system may have implications for long-term access of nutrients and hormones and therefore the control of skeletal muscle metabolism and contractile performance.

There is evidence for non-nutritive flow routes within, or associated with, skeletal muscle. Large capillary-like structures are possible candidates. The proportion of flow distributed between nutritive and non-nutritive routes appears to be tightly regulated and can control muscle metabolism and contraction by regulating delivery and product removal. The portion of flow that is carried by the non-nutritive routes at rest affords a flow reserve for amplifying nutrient delivery as muscle begins to work and may determine post-exercise metabolism. Inappropriate signals, however, may diminish nutritive flow to the detriment of muscle performance and post-exercise recovery. New technologies should allow the identification of the non-nutritive routes.

Hindlimbs of mature age obese fa/fa Zucker rats were perfused and found to be markedly insulin-resistant when compared to the hindlimbs of age-matched lean Fa/? animals. Hindlimb analysis also showed a greater content of fat and a lower content of muscle in the obese. Treatment of the obese animals for 7 days with the thiazolidinedione, BRL 49653 (3 mumol/kg/day) significantly decreased the insulin resistance of the hindlimb and significantly increased the rate of weight gain in the whole rat. However, the decreased insulin resistance due to BRL 49653 could not be accounted for by an increase in the proportion of hindlimb muscle to fat or by an increase in the hindlimb muscle mass perfused.

Endocrine stimulation of muscle nonshivering thermogenesis (NST) in ducklings was investigated in vitro using a perfused hindlimb preparation maintained at 25°C. Effects of flow rate, norepinephrine (NE), epinephrine, and glucagon on perfused muscle oxygen consumption (M˙o 2) and perfusion pressure were studied. Control ducklings ( Cairina moschata, 5 wk old) reared at thermoneutrality (25°C, TN) were compared with two age-matched groups exhibiting muscle NST in vivo: cold-acclimated ducklings (4°C, 4 wk, CA) and glucagon-treated ducklings (103 nmol/kg twice daily, intraperitoneally, GT). BasalM˙o 2was higher in CA than in TN or GT ducklings and increased in all groups with elevated flow rates. Catecholamines increased bothM˙o 2and perfusion pressure. The maximal effect onM˙o 2was higher in CA (+36%) and GT ducklings (+43%) than in controls (+31%), but was associated with reduced vasoconstriction. Flow rate did not consistently potentiate the NE response. At high doses, catecholamines became inhibitory onM˙o 2while a monotonous increase of pressure was still observed. Glucagon, by contrast, slightly decreased bothM˙o 2and pressure. This vasodilatory effect was greater in CA ducklings than controls in preconstricted preparations. In vivo, low-dose epinephrine induced a modest thermogenic effect (+10%) in CA ducklings. These findings showed that duckling muscle thermogenesis is directly stimulated in vitro by catecholamines but not by glucagon. Higher in vitro thermogenic effects of NE in ducklings that were expected to exhibit muscle NST in vivo suggests catecholamine involvement in muscle NST in vivo. Potential vascular control of avian muscle NST is discussed.

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