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The isolated rat hindlimb was perfused with Krebs-bicarbonate buffer without erythrocytes and albumin in a flow-through mode at 32 degrees C, and the viability and metabolic characteristics of perfused skeletal muscle were examined. 1) With the flow rate at 15 ml X min-1 X leg-1, glucose and O2 uptake, lactate release, lactate-to-pyruvate ratio in effluent, and tissue creatine phosphate and adenine nucleotides remained constant at rest during perfusion for 90 min. The twitch tension changed little over perfusion. 2) When the leg was stimulated at a frequency below 0.5 Hz, the standard flow rate adequately delivered O2 to the perfused leg. Sciatic nerve stimulation enhanced glucose uptake in the absence of insulin. 3) The stimulatory effect of insulin on glucose uptake was observed with a concentration as low as 0.1 mU/ml, and maximal effect was at approximately mU/ml, with a nearly eightfold increase in glucose uptake. 4) Epinephrine and isoproterenol at a concentration of 0.5 nM stimulated lactate release, with maximal effect at 5 nM. The response to catecholamines was reversible and reproducible with a single preparation during the perfusion period of 120 min. The results indicated that the perfusion of hindlimb with a hemoglobin- and albumin-free medium is a convenient and reliable tool for the biochemical investigations of the integral function of hindlimb skeletal muscle.
The effect of norepinephrine on the consumption of O2 was studied in the skeletal muscle in the perfused hindlimbs of rats that had been kept at 4 degrees C for 5-25 days. 1) Basal rates of consumption of O2 and release of lactate were not affected by exposure to cold. 2) The stimulation of consumption of O2 by norepinephrine increased in the perfused hindlimbs of rats exposed to cold for 10-25 days, with a maximum stimulation at 20 days. The response to norepinephrine decreased markedly in hindlimbs perfused with propranolol or phentolamine. Phenylephrine, in the presence of 0.5 nM isoproterenol, stimulated the consumption of O2 at concentrations as low as 0.5 microM, with a maximum at 5 microM, in hindlimbs from the group exposed to cold for 20 days. 3) Ouabain inhibited the stimulation of consumption of O2 by norepinephrine. Norepinephrine caused a net release of K+ in control muscle but a net uptake of K+ by muscle from the group exposed to cold for 20 days. The results suggest that the calorigenic responsiveness to norepinephrine increases in skeletal muscle during acclimation of the rat to the cold, both alpha- and beta-adrenergic actions are involved in the calorigenic effects of norepinephrine, and the increased activity of the Na+-K+ ATPase under the influence of norepinephrine may be involved in the calorigenic action of norepinephrine on the skeletal muscle of cold-acclimated rats.
This study was performed to examine, first, the protective effects and responses of collateral vessels of the hind limb in normal and atherosclerotic monkeys and, second, the effects of chronic arterial occlusion on the development of atherosclerosis. The iliac artery was ligated on one side in cynomolgus monkeys. Sixteen months later, we recorded the pressure gradient across the limb collaterals and measured blood flow with microspheres. Collateral conductance was fivefold greater after chronic ligation of the iliac artery than after acute ligation. Despite dilatation or growth of collateral vessels after chronic ligation, iliac pressure was reduced distal to the ligation. Blood flow to the limb was normal after chronic ligation in both normal and atherosclerotic monkeys. Collateral vessels constricted in response to infusion of phenylephrine and serotonin in normal and atherosclerotic monkeys. Thus, one conclusion of this study is that collateral vessels restore limb blood flow to normal after chronic vascular occlusion in both normal and atherosclerotic monkeys, but the protective effects of collateral vessels may be compromised by vasoconstrictor stimuli. Morphometric measurements indicated that occlusion of the iliac artery reduced proliferation of atherosclerotic intima distal to the occlusion in the cholesterol-fed monkeys. Thus, a second conclusion of this study is that atherosclerosis is attenuated below an arterial occlusion.
The effects of isoproterenol on the release of alanine during perfusion with pyruvate and valine were studied in perfused hindlimbs from rats that had been kept for 5 or 20 days at 4 degrees C. In hindlimbs perfused with Krebs bicarbonate buffer in a flow-through mode, the rate of release of alanine during perfusion with 2 mM pyruvate plus 5 mM valine was 250 nmol.min-1.leg-1, a rate that is comparable with that reported in hindlimbs perfused with complex medium. Neither the pyruvate-stimulated nor valine plus pyruvate-stimulated rates of release of alanine changed after 20 days of exposure to cold. Isoproterenol inhibited the release of alanine during perfusion with pyruvate, with valine, and with valine plus pyruvate in hindlimbs from a control group of rats. However, in hindlimbs from cold-exposed groups, isoproterenol failed to inhibit the release of alanine during perfusion with valine plus pyruvate and stimulated the release of alanine during perfusion with valine. Aminooxyacetate inhibited the effects of valine, pyruvate, and isoproterenol. The results obtained suggested that cold exposure decreases the responses to isoproterenol of the mechanism of alanine release and causes an increased supply of alanine to the liver.
This study measured the hemodynamics of peripheral arterial sites in the rat, using 20 MHz pulsed ultrasonic Doppler velocimeter (PUDVM) methods. The lower extremities of 14 male Sprague-Dawley rats were studied. The targeted sites included the abdominal aorta, external iliac, proximal femoral, mid-femoral, and saphenous arteries. The hemodynamic variables of pulse period, maximum centerline velocity, lumen diameter, and mean volumetric flow were calculated interactively from temporal-spatial plots of local velocity distributions. An analysis of variance revealed significant differences between right and left sides for lumen diameter (P = 0.028) and mean volumetric flow (P less than 0.0001). The analysis showed no statistical difference for pulse period (P = 0.0836) among sites. However, three distinct groupings of sites: 1) abdominal aorta, 2) external iliac, proximal femoral, and mid-femoral arteries, and 3) saphenous artery were noted for the remaining hemodynamic variables (P less than 0.05). These results indicate that three hemodynamically distinct regions are available for microvascular research in the rat lower extremity arterial tree.
To assess the means by which peripheral metabolism facilitates the transition to a gluconeogenic state, dogs were studied during 150 min of moderate treadmill exercise. Metabolism in the working hindlimb was assessed with arteriovenous difference and isotopic techniques (n = 9). In a separate group (n = 6), hepatic metabolism was assessed using arteriovenous differences. Limb glucose uptake (LGU) and oxidation (GOX) rose from 33 +/- 10 and 5 +/- 2 to 101 +/- 20 and 54 +/- 15 mumol/min at 10 min of exercise. LGU continued to rise (151 +/- 21 mumol/min at 150 min), while GOX declined. Nonoxidative glucose metabolism (GNOX) was 28 +/- 10 mumol/min at rest and 47 +/- 24 and 108 +/- 16 mumol/min at 10 and 150 min of exercise. Limb nonglycemic (predominantly glycogen) pyruvate formation rose from 52 +/- 22 to 198 +/- 54 and 242 +/- 74 mumol/min at 10 and 150 min of exercise. The gradual increase in GNOX and the high glycogenolytic rate were paralleled by accelerated lactate, pyruvate, and glutamine releases. Limb glycerol release rose promptly and remained elevated during exercise. Plasma nonesterified fatty acids (NEFAs) rose gradually and paralleled the gradual rise in GNOX (r = 0.93). The resulting rise in hepatic NEFA delivery was highly correlated to hepatic O2 uptake (r = 0.87), hepatic vein lactate-to-pyruvate ratio (r = 0.90), and intrahepatic gluconeogenic efficiency (r = 0.96). In summary, during exercise, 1) the primary fate of the added glucose consumed by the working limb is initially oxidation, but becomes GNOX as exercise duration progresses; 2) glycogenolysis rises promptly, but attains its highest rate at the end of exercise; 3) the late increases in GNOX and glycogenolysis relate to an increased gluconeogenic precursor release from the working limb; 4) although lipolysis increases promptly and is sustained, circulating NEFAs rise only gradually; and 5) the gradual rise in plasma NEFAs is highly correlated to the shift from GOX to GNOX and the adjustments in hepatic metabolism that are necessary for the full gluconeogenic response.