Low-intensity training produces muscle adaptations in rats with femoral artery stenosis.

The effectiveness of a mild-intensity exercise program to induce adaptations within skeletal muscle of animals with peripheral arterial insufficiency was evaluated using an isolated perfused hindlimb preparation at a muscle blood flow similar to the peak found in vivo. Adult rats were subjected to bilateral femoral artery stenosis sufficient to limit peak blood flow during exercise but not alter resting blood flow. Stenosed-trained (Sten-Trained) rats walked on a treadmill at an easily achieved speed (20 m/min with a 15% grade) 5 days wk. Exercise tolerance improved from 10 min initially to 2 h/day. Non-stenosed-sedentary (Non-Sten-Sed) and stenosed-sedentary (Sten-Sed) animals were limited to cage activity. Oxygen delivery to the contracting muscles was similar among groups (7.0 +/- 0.4, 7.3 +/- 0.6, and 6.6 +/- 0.6 mumol.min-1.g-1 in Non-Sten-Sed, Sten-Sed, and Sten-Trained, respectively; n = 13 each). Force development was better maintained by Sten-Trained muscle (P less than 0.001) during a sequence of tetanic contraction conditions. Peak oxygen consumption was greater (P less than 0.05) in the Sten-Trained (5.23 +/- 0.34 mumol.min-1.g-1) than in Non-Sten-Sed (4.08 +/- 0.35) and Sten-Sed (4.34 +/- 0.37) rats. The increased peak oxygen extraction (P less than 0.05) by the muscle of the Sten-Trained rats (82.5 +/- 7.1% of oxygen inflow vs. 58.7 +/- 4.7 and 57.4 +/- 5.0%, respectively) was probably related to the increased muscle capillarity and mitochondrial enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle glucose uptake of obese Zucker rats trained at two different intensities

Exercise training reduces the muscle insulin resistance of the obese Zucker rat. The purpose of the present study was to determine whether the magnitude of this training response is exercise intensity specific. Obese Zucker rats were randomly divided into sedentary (SED), low-intensity (LI), and high-intensity (HI) exercise groups. For the LI rats, exercise training consisted of running on a rodent treadmill at 18 m/min up an 8% grade for 90 min. Rats in the HI group ran at 24 m/min up an 8% grade for four 17-min bouts with 3 min between bouts. Both exercise groups performed the same amount of work and trained 5 days/wk for 7 wk. To evaluate muscle insulin resistance, rat hindlimbs were perfused for 30 min with perfusate containing 6 mM glucose (0.15 mu Ci of D-[14C(U)] glucose/ml) and either a maximal (10.0 mU/ml) or a submaximal (0.50 mU/ml) insulin concentration. Perfusions were performed 48-56 h after the last exercise bout and a 12-h fast. In the presence of 0.5 mU/ml insulin, the rate of muscle glucose uptake was found to be significantly faster for the HI (9.56 +/- 0.66 mumol.h-1.g-1) than for the LI (7.72 +/- 0.65 mumol.h-1.g-1) and SED (6.64 +/- 0.44 mumol.h-1.g-1) rats. The difference in glucose uptake between the LI and SED rats was not significant. In the presence of 10.0 mU/ml insulin, the rate of glucose uptake was significantly faster for the HI (16.43 +/- 1.02 mumol.h-1.g-1) than for the LI rats (13.76 +/- 0.84 mumol.h-1.g-1) and significantly faster for the LI than for the SED rats (11.02 +/- 0.35 mumol.h-1.g-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of reduced cytochrome oxidase activity on peak oxygen consumption of muscle

The impact of reduced muscle oxidative capacity on peak oxygen consumption and isometric performance was evaluated using an isolated rat hindlimb preparation perfused with a high oxygen delivery. Capacity for electron transport was reduced with chloramphenicol (CAP), an inhibitor of mitochondrial gene-coded protein synthesis. The activity of cytochrome oxidase, a mitochondrial cristae component, was reduced approximately 45% (P less than 0.005) in the mixed-fiber-type plantaris muscle. Several facets of muscle remodeling were also evident with the 10- to 14-day CAP treatment, including decreased citrate synthase activity, increased capillarity, and increased numbers of type IIc fibers. Perfusion of CAP (n = 6) and control (n = 7) rat hindlimbs of similar size with similar total flows (10-11 ml/min) and oxygen contents (20-21 vol%) resulted in similarly high oxygen deliveries to contracting muscles of the hindlimbs (CAP, 9.66 +/- 0.83 mumols.min-1.g-1; control, 8.74 +/- 0.75). Performance of the gastrocnemius-plantaris-soleus group declined in a similar fashion for both groups during increasingly intense near-steady-state tetanic contraction (100 ms at 100 Hz) conditions of 4, 8, 15, 30, 45, and 60 per minute. Oxygen consumption was similar for both groups at rest and increased similarly at each contraction condition. Peak oxygen consumption was not different between CAP (5.34 +/- 0.55 mumols.min-1.g-1) and control (5.74 +/- 0.43) groups and required only 56-68% of the oxygen delivered. This implies that rat skeletal muscle can suffer a significant reduction in its electron transport capacity without impairing peak oxygen consumption and muscle performance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of training on blood flow to different skeletal muscle fiber types

Blood flows to fast-twitch red (FTR), fast-twitch white (FTW), and slow-twitch red (STR) fiber sections of the gastrocnemius-soleus-plantaris muscle group of sedentary and trained rats were determined using radiolabeled microspheres during the 1st and 10th min of in situ contractions at frequencies ranging from 7.5 to 90 tetani/min. Treadmill training increased the cytochrome c content of both FTW (6.0 +/- 0.13 nmol/g to 12.2 +/- 0.27) and FTR (22.2 +/- 0.32 to 26.7 +/- 0.25) muscle. Loss of tension, evident at 15 tetani/min and above, was less (P less than 0.001) in trained animals. Although steady-state blood flows (10th min) to FTR and STR fibers were not altered by training, initial flows (1st min) to the trained FTR section were greater (P less than 0.025). Overall initial flows to both red fiber types were excessively high at the easier contraction conditions, but subsequently declined to values more reflective of the expected energy demands. This time-dependent relative hyperemia was not found in either sedentary or trained FTW muscle. However, training increased the maximal blood flow in the FTW sections [60 +/- 3.2 (n = 36) vs. 88 +/- 5.2 ml X min X 100 g-1 (n = 36)]. This 40-50% increase in FTW blood flow would produce only a modest 10% increase in blood flow to a whole mixed-fiber muscle, since the flow capacity of the FTW muscle is only one third to one fourth that of FTR muscle. This overall increase in blood flow, however, is similar to changes in VO2max found in trained rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial flow distribution. II : Empty beating heart, ventricular fibrillation and cardiac arrest

Myocardial oxygen consumption (MVO2) and coronary blood flow (CBF) distribution were studied in 21 isolated, metabolically supported dog hearts. Measurements of MVO2 and CBF distribution were carried out in three different experimental conditions : empty beating heart (EBH), ventricular fibrillation (VF) and high potassium-induced cardiac arrest (CA). MVO2 was approximately the same in EBH and VF (4.09 +/- 0.77 and 4.28 +/- 0.68 ml O2 min-1 100 g-1 respectively), and significantly lower in the group with CA (2.40 +/- 0.18 ml O2 min-1 100 g-1, P less than 0.05). Total CBF showed no significant differences among the three groups (84 +/- 7 ml/min in EBH; 78 +/- 7 ml/min in VF and 83 +/- 7 ml/min in CA). Subendocardial CBF per unit of tissue mass was significantly lower in hearts with VF (0.43 +/- 0.01 ml/min-1 g-1, P less than 0.05) when tested against the other two groups of experiments (0.69 +/- 0.03 ml min-1 g-1 in EBH and 0.65 +/- +/- 0.04 ml min-1 g-1 in CA). This was also reflected in the endo/epi ratio, that was significantly lower in VF (1.41 +/- 0.07, P less than 0.05) with respect to the other two groups (2 +/- 0.09 in EBH and 2.21 +/- 0.07 in CA). From data presented here we can conclude that cardioplegia, even in absence of hypothermia, is a method that will assure myocardial protection providing : (1) a lower subendocardial MVO2; (2) a higher subendocardial CBF, which helps for a prompt recovery during reperfusion.     

Distribution of blood flow in muscles of miniature swine during exercise

The purpose of this study was to determine how the distribution of blood flow within and among the skeletal muscles of miniature swine (22 +/- 1 kg body wt) varies as a function of treadmill speed. Radiolabeled microspheres were used to measure cardiac output (Q) and tissue blood flows in preexercise and at 3-5 min of treadmill exercise at 4.8, 8.0, 11.3, 14.5, and 17.7 km/h. All pigs (n = 8) attained maximal O2 consumption (VO2max) (60 +/- 4 ml X min-1 X kg-1) by the time they ran at 17.7 km/h. At VO2max, 87% of Q (9.9 +/- 0.5 l/min) was to skeletal muscle, which constituted 36 +/- 1% of body mass. Average total muscle blood flow at VO2max was 127 +/- 14 ml X min-1 X 100 g-1; average limb muscle flow was 135 +/- 17 ml X min-1 X 100 g-1. Within the limb muscles, blood flow was distributed so that the deep red parts of extensor muscles had flows about two times higher than the more superficial white portions of the same muscles; the highest muscle blood flows occurred in the elbow flexors (brachialis: 290 +/- 44 ml X min-1 X 100 g-1). Peak exercise blood flows in the limb muscles were proportional (P less than 0.05) to the succinate dehydrogenase activities (r = 0.84), capillary densities (r = 0.78), and populations of oxidative (slow-twitch oxidative + fast-twitch oxidative-glycolytic) fiber types (r = 0.93) in the muscles. Total muscle blood flow plotted as a function of exercise intensity did not peak until the pigs attained VO2max, although flows in some individual muscles showed a plateau in this relationship at submaximal exercise intensities. The data demonstrate that blood flow in skeletal muscles of miniature swine is distributed heterogeneously and varies in relation to fiber type composition and exercise intensity.     

Downhill treadmill running trains the rat spinotrapezius muscle.

There are currently no models of exercise that recruit and train muscles, such as the rat spinotrapezius, that are suitable for transmission intravital microscopic investigation of the microcirculation. Recent experimental evidence supports the concept that running downhill on a motorized treadmill recruits the spinotrapezius muscle of the rat. Based on these results, we tested the hypothesis that 6 wk of downhill running (-14 degrees grade) for 1 h/day, 5 days/wk, at a speed of up to 35 m/min, would 1) increase whole body peak oxygen uptake (Vo(2 peak)), 2) increase spinotrapezius citrate synthase activity, and 3) reduce the fatigability of the spinotrapezius during electrically induced 1-Hz submaximal tetanic contractions. Trained rats (n = 6) elicited a 24% higher Vo(2 peak) (in ml.min(-1).kg(-1): sedentary 58.5 +/- 2.0, trained 72.7 +/- 2.0; P < 0.001) and a 41% greater spinotrapezius citrate synthase activity (in mumol.min(-1).g(-1): sedentary 14.1 +/- 0.7, trained 19.9 +/- 0.9; P < 0.001) compared with sedentary controls (n = 6). In addition, at the end of 15 min of electrical stimulation, trained rats sustained a greater percentage of the initial tension than their sedentary counterparts (control 34.3 +/- 3.1%, trained 59.0 +/- 7.2%; P < 0.05). These results demonstrate that downhill running is successful in promoting training adaptations in the spinotrapezius muscle, including increased oxidative capacity and resistance to fatigue. Since the spinotrapezius muscle is commonly used in studies using intravital microscopy to examine microcirculatory function at rest and during contractions, our results suggest that downhill running is an effective training paradigm that can be used to investigate the mechanisms for improved microcirculatory function following exercise training in health and disease.     

Methylene blue inhibits hypoxic cerebral vasodilation in awake sheep.

Cerebral vasodilation in hypoxia may involve endothelium-derived relaxing factor-nitric oxide. Methylene blue (MB), an in vitro inhibitor of soluble guanylate cyclase, was injected intravenously into six adult ewes instrumented chronically with left ventricular, aortic, and sagittal sinus catheters. In normoxia, MB (0.5 mg/kg) did not alter cerebral blood flow (CBF, measured with 15-microns radiolabeled microspheres), cerebral O2 uptake, mean arterial pressure (MAP), heart rate, cerebral lactate release, or cerebral O2 extraction fraction (OEF). After 1 h of normobaric poikilocapnic hypoxia (arterial PO2 40 Torr, arterial O2 saturation 50%), CBF increased from 51 +/- 5.8 to 142 +/- 18.8 ml.min-1 x 100 g-1, cerebral O2 uptake from 3.5 +/- 0.25 to 4.7 +/- 0.41 ml.min-1 x 100 g-1, cerebral lactate release from 2 +/- 10 to 100 +/- 50 mumol.min- x 100 g-1, and heart rate from 107 +/- 5 to 155 +/- 9 beats/min (P < 0.01). MAP and OEF were unchanged from 91 +/- 3 mmHg and 48 +/- 4%, respectively. In hypoxia, 30 min after MB (0.5 mg/kg), CBF declined to 79.3 +/- 11.7 ml.min-1 x 100 g-1 (P < 0.01), brain O2 uptake (4.3 +/- 0.9 ml.min-1 x 100 g-1) and heart rate (133 +/- 9 beats/min) remained elevated, cerebral lactate release became negative (-155 +/- 60 mumol.min-1 x 100 g-1, P < 0.01), OEF increased to 57 +/- 3% (P < 0.01), and MAP (93 +/- 5 mmHg) was unchanged. The sheep became behaviorally depressed, probably because of global cerebral ischemia. These results may be related to interference with a guanylate cyclase-dependent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Training increases muscle blood flow in rats with peripheral arterial insufficiency

This study investigated the effect of physical training on muscle blood flow (BF) in rats with peripheral arterial insufficiency during treadmill running. Bilateral stenosis of the femoral artery of adult rats (300-350 g) was performed to reduce exercise hyperemia in the hindlimb but not limit resting muscle BF. Rats were divided into normal sedentary, acute stenosed (stenosed 3 days before the experiment), stenosed sedentary (limited to cage activity), and stenosed trained (run on a treadmill by a progressively intense program, up to 50-60 min/day, 5 days/wk for 6-8 wk). Hindlimb BF was determined with 85Sr- and 141Ce-labeled microspheres at a low (20 m/min) and high treadmill speed (30-40 m/min depending on ability). Maximal hindlimb BF was reduced to approximately 50% normal in the acute stenosed group. Total hindlimb BF (81 +/- 5 ml.min-1.100 g-1) did not change in stenosed sedentary animals with 6-8 wk of cage activity, but a redistribution of BF occurred within the hindlimb. Two factors contributed to a higher BF to the distal limb muscle of the trained animals. A redistribution BF within the hindlimb occurred in stenosed trained animals; distal limb BF increased to approximately 80% (P less than 0.001) of the proximal tissue. In addition, an increase in total hindlimb BF with training indicates that collateral BF has been enhanced (P less than 0.025). The associated increase in oxygen delivery to the relatively ischemic muscle probably contributed to the markedly improved exercise tolerance evident in the trained animals.     

Maximal vascular leg conductance in trained and untrained men

Lower leg blood flow and vascular conductance were studied and related to maximal oxygen uptake in 15 sedentary men (28.5 +/- 1.2 yr, mean +/- SE) and 11 endurance-trained men (30.5 +/- 2.0 yr). Blood flows were obtained at rest and during reactive hyperemia produced by ischemic exercise to fatigue. Vascular conductance was computed from blood flow measured by venous occlusion plethysmography, and mean arterial blood pressure was determined by auscultation of the brachial artery. Resting blood flow and mean arterial pressure were similar in both groups (combined mean, 3.0 ml X min-1 X 100 ml-1 and 88.2 mmHg). After ischemic exercise, blood flows were 29- and 19-fold higher (P less than 0.001) than rest in trained (83.3 +/- 3.8 ml X min-1 X 100 ml-1) and sedentary subjects (61.5 +/- 2.3 ml X min-1 X 100 ml-1), respectively. Blood pressure and heart rate were only slightly elevated in both groups. Maximal vascular conductance was significantly higher (P less than 0.001) in the trained compared with the sedentary subjects. The correlation coefficients for maximal oxygen uptake vs. vascular conductance were 0.81 (trained) and 0.45 (sedentary). These data suggest that physical training increases the capacity for vasodilation in active limbs and also enables the trained individual to utilize a larger fraction of maximal vascular conductance than the sedentary subject.     

V(O2) max is unaffected by altering the temporal pattern of stimulation frequency in rat hindlimb in situ.

It might be anticipated that fatiguing contractions would impair the aerobic metabolic response in skeletal muscle if significant fatigue developed before full activation of aerobic metabolism. On the basis of this premise, we examined two groups of rats to test the hypothesis that a gradual increase in stimulation frequency would yield a higher maximal O2 uptake (Vo2 max) than beginning immediately with an intense stimulation frequency because of a slower progression of fatigue under the former conditions. In one group of animals, the distal hindlimb muscles were electrically stimulated at a frequency of 60 tetani/min for 4 min (F60; n = 6 rats); in the other group, the muscles were incrementally stimulated for 1 min at each of 7.5, 15, 30, and 60 tetani/min and for 2 min at 90 tetani/min (FInc; n = 5 rats). Despite large differences in rate of fatigue [time to 60% of initial force was 47 +/- 3 (SE) vs. 188 +/- 1 s in F60 and FInc, respectively] and the time at which Vo2 max occurred (120 +/- 15 vs. 264 +/- 6 s), Vo2 max was not different (419 +/- 24 vs. 381 +/- 44 micromol x min-1. 100 g-1). Furthermore, time x tension integral at Vo2 max (3.82 +/- 0.41 vs. 4.07 +/- 0.31 N. s) and peak lactate efflux (910 +/- 45 vs. 800 +/- 98 micromol x min-1. 100 g-1) were not different between groups. Thus our results show that the more rapid progression of fatigue in F60 did not compromise the aerobic metabolic response in electrically stimulated rat hindlimb muscles. However, in both groups, O2 uptake and lactate efflux declined after Vo2 max was attained in similar proportion to a further fall in force, suggesting that ongoing fatigue with intense contractions reduced ATP demand below that requiring maximal aerobic and glycolytic metabolic responses once Vo2 max was reached.     

Differences between VO2 maxima of twitch and tetanic contractions are related to blood flow

The purpose of this investigation was to compare oxygen uptake (VO2) and fatigue characteristics of isotonic tetanic contractions with those observed during isotonic twitches in dog gastrocnemius-plantaris muscle. Tetanic contractions (1/s, 200-ms trains of 50 impulses/s) elicited a peak VO2 of 9.01 +/- 0.42 mumol.g-1.min-1, which declined 29% in 30 min. The peak was significantly lower during 4/s twitches (6.23 +/- 0.36 mumol.g-1.min-1), but the rate of decline was similar. Peak blood flow (Q) was 37% higher and decreased more slowly during tetanic than twitch contractions. VO2/Q and VO2/venous PO2 were similar in both groups at peak VO2 and later declined or remained constant over time. Power was significantly greater with tetanic contractions with the relative decline between 3 and 30 min similar in both groups (32 and 37%). In conclusion, tetanic contractions result in significantly higher VO2 and power than do twitch contractions. This was derived primarily from increased Q because the arteriovenous O2 difference was similar. A significant determinant of the difference in Q between twitch and tetanic contractions is mechanical hindrance of Q. There is relatively more time for unhindered flow in the tetanic contractions. In electrically stimulated muscles, maximal VO2 is related to Q and reflects mainly Q through the muscle rather than the VO2 capacity of the muscle.     

Regional differences in blood flow and oxygen consumption in resting muscle and their relationship during recovery from exhaustive exercise.

This investigation evaluated regional differences in blood flow and oxygen consumption and their relationship in exercised muscle during recovery from exhaustive exercise. Five healthy men performed exhaustive one-legged cycling exercise. Positron emission tomography was used to measure blood flow, oxygen uptake, and oxygen extraction in the quadriceps femoris muscle before and after exercise. Regions of interest included five areas of the muscle (two proximal, one central, and two distal), which were evenly spaced across the muscle. Before exercise, blood flow and oxygen consumption decreased significantly (P < 0.05) in the direction from the proximal to the distal portions; blood flow declined from 2.0 +/- 0.5 to 1.4 +/- 0.3 ml x 100 g-1 x min-1, and oxygen consumption decreased from 0.21 +/- 0.04 to 0.17 +/- 0.02 ml.100 g-1x min-1. In contrast, these gradients in blood flow and oxygen consumption diminished during recovery after exercise. Consequently, there was a positive relationship between changes in blood flow and oxygen consumption in an exercised muscle during recovery after exercise (r = 0.963, P < 0.01). These changes became larger in the direction from proximal to distal portions: blood flow increased from 2.9 +/- 0.7 to 3.9 +/- 0.8 and oxygen consumption from 1.4 +/- 0.1 to 1.8 +/- 0.4 times resting values. These results suggest that hemodynamic variables are heterogeneous within a muscle both at rest and during recovery from exercise and that there is a systematic difference in these variables in the direction from proximal to distal regions within the quadriceps femoris muscle.     

N omega-nitro-L-arginine influences cerebral metabolism in awake sheep.

Cerebral vasodilation in hypoxia may involve endothelium-derived relaxing factor-nitric oxide (NO). An inhibitor of NO formation, N omega-nitro-L-arginine (LNA, 100 micrograms/kg i.v.), was given to conscious sheep (n = 6) during normoxia and again in hypocapnic hypoxia (arterial PO2 approximately 38 Torr). Blood samples were obtained from the aorta and sagittal sinus, and cerebral blood flow (CBF) was measured with 15-microns radiolabeled microspheres. During normoxia, LNA elevated (P < 0.05) mean arterial pressure from 82 +/- 3 to 88 +/- 2 (SE) mmHg and cerebral perfusion pressure (CPP) from 72 +/- 3 to 79 +/- 3 mmHg, CBF was unchanged, and cerebral lactate release (CLR) rose temporarily from 0.0 +/- 1.9 to 13.3 +/- 8.7 mumol.min-1 x 100 g-1 (P < 0.05). The glucose-O2 index declined (P < 0.05) from 1.67 +/- 0.16 to 1.03 +/- 0.4 mumol.min-1 x 100 g-1. Hypoxia increased CBF from 59.9 +/- 5.4 to 122.5 +/- 17.5 ml.min-1 x 100 g-1 and the glucose-O2 index from 1.75 +/- 0.43 to 2.49 +/- 0.52 mumol.min-1 x 100 g-1 and decreased brain CO2 output, brain respiratory quotient, and CPP (all P < 0.05), while cerebral O2 uptake, CLR, and CPP were unchanged. LNA given during hypoxia decreased CBF to 77.7 +/- 11.8 ml.min-1 x 100 g-1 and cerebral O2 uptake from 154 +/- 22 to 105.2 +/- 12.4 mumol.min-1 x 100 g-1 and further elevated mean arterial pressure to 98 +/- 2 mmHg (all P < 0.05), CLR was unchanged, and, surprisingly, brain CO2 output and respiratory quotient were reduced dramatically to negative values (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Dopamine production by the isolated perfused rat kidney

We used isolated perfused rat kidneys to examine dopamine (DA) production and its relation to renal function. Both innervated and chronically surgically denervated kidneys perfused with a solution containing neither albumin nor tyrosine, excreted 0.2 +/- 0.1 ng DA X min-1 X g wet weight-1 during the 10-min collection period between 30 and 40 min after starting perfusion. When perfused with 6.7% albumin, without tyrosine, innervated kidneys excreted 1.0 +/- 0.06 ng DA X min-1 X g-1 and denervated kidneys excreted 1.0 +/- 0.07 DA X min-1 X g-1. When 0.03 mM tyrosine was included in the albumin perfusate, innervated kidneys excreted 1.2 +/- 0.1 ng DA X min-1 X g-1 (p less than 0.1). Under these conditions DA excretion continued for at least 100 min at which time it was 0.6 ng X min-1 X g-1 and 86 ng/g kidney weight had been excreted. Denervated kidneys perfused with albumin + tyrosine excreted 0.9 +/- 0.13 ng DA X min-1 X g-1. Renal stores of free DA, conjugated DA, and dihydroxyphenylalanine (DOPA) could have provided at the most 30 ng/g of DA. Carbidopa inhibited DA excretion completely. DA excretion did not correlate with renal vascular resistance, inulin clearance, or fractional sodium excretion. In summary, nonneural tissue in isolated perfused kidneys produced DA at the same rate as denervated kidneys in vivo. Less than one-third of the DA produced by isolated kidneys could have come from intrarenal stores of DOPA, free DA, and conjugated DA; the rest was synthesized from unknown precursors.(ABSTRACT TRUNCATED AT 250 WORDS)     

O2 delivery at VO2max and oxidative capacity in muscles of standardbred horses.

The purpose of this study was to describe the relationships between 16 physiological, biochemical, and morphological variables presumed to relate to the oxidative capacity in quadriceps muscles or muscle parts in Standardbred horses. The variables included O2 delivery (blood flow) and mean capillary transit time (MTT) during treadmill locomotion at whole animal maximal O2 consumption (VO2max, 134 +/- 2 ml.min-1 x kg-1), capillary density and capillary-to-fiber ratio, myoglobin concentration, oxidative enzyme activities, glycolytic enzyme activities, fiber type populations, and fiber size. These components of muscle metabolic capacity were found to be interrelated to varying degrees using correlation matrix analysis, with lactate dehydrogenase activity showing the most significant correlations (n = 14) with other variables. Most of the "oxidative" variables occurred in the highest quantities in the deepest muscle of the group (vastus intermedius) and in the deepest parts of the other quadriceps muscles where the highest proportions of type I fibers were localized. The highest blood flow measured with microspheres in the muscle group during exercise was in vastus intermedius muscle (145 ml.min-1 x 100 g-1), and the lowest was in the superficial part of rectus femoris muscle (32 ml.min-1 x 100 g-1). Average muscle blood flow during exercise at whole animal VO2max was 116 ml.min-1 x 100 g-1. Because skeletal muscle comprised 43% of total body mass (453 +/- 34 kg), total muscle blood flow was estimated at 226 l/min, which was approximately 78% of total cardiac output (288 l/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of increased Hb-O2 affinity on VO2max at constant O2 delivery in dog muscle in situ

We investigated the effect of increasing hemoglobin- (Hb) O2 affinity on muscle maximal O2 uptake (VO2max) while muscle blood flow, [Hb], HbO2 saturation, and thus O2 delivery (muscle blood flow X arterial O2 content) to the working muscle were kept unchanged from control. VO2max was measured in isolated in situ canine gastrocnemius working maximally (isometric tetanic contractions). The muscles were pump perfused, in alternating order, with either normal blood [O2 half-saturation pressure of hemoglobin (P50) = 32.1 +/- 0.5 (SE) Torr] or blood from dogs that had been fed sodium cyanate (150 mg.kg-1.day-1) for 3-4 wk (P50 = 23.2 +/- 0.9). In both conditions (n = 8) arterial PO2 was set at approximately 200 Torr to fully saturate arterial blood, which thereby produced the same arterial O2 contents, and muscle blood flow was set at 106 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. VO2max was 11.8 +/- 1.0 ml.min-1.100 g-1 when perfused with the normal blood (control) and was reduced by 17% to 9.8 +/- 0.7 ml.min-1.100 g-1 when perfused with the low-P50 blood (P less than 0.01). Mean muscle effluent venous PO2 was also significantly less (26 +/- 3 vs. 30 +/- 2 Torr; P less than 0.01) in the low-P50 condition, as was an estimate of the capillary driving pressure for O2 diffusion, the mean capillary PO2 (45 +/- 3 vs. 51 +/- 2 Torr). However, the estimated muscle O2 diffusing capacity was not different between conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of exercise training on aortic collagen content in spontaneously hypertensive rats (SHR)

We investigated the effects of exercise training on the amount of aortic collagen and systolic blood pressure in spontaneously hypertensive rats (SHR). Ten-week old SHR were trained either by forced treadmill running (26.8 m X min-1 -1 h X day-1, five times a week, 0% incline) or by voluntary running in revolving wheels (7,800 m X day-1 at peak) for 8 weeks. Succinate dehydrogenase (SDH) activity measured as a marker of an endurance training effect was 13% higher (P less than 0.01) in the soleus of forced-exercised animals than in that of sedentary ones. (6.56 +/- 0.17 mumol X g-1 X min-1; mean +/- SEM), whereas SDH activity in that of voluntarily-exercised group was found to be at the same level as in sedentary animals. The systolic blood pressure after training increased by 26.4 in sedentary, 21.1 in voluntarily-exercised, and 33.9 mm Hg in forced-exercised rats, when compared with the value of each group at the beginning of the training program. A significant difference was observed in the increment of blood pressure only between the voluntarily- and forced-exercised groups (P less than 0.05). The amount of aortic collagen in voluntarily-trained rats (96.5 +/- 2.0 mg X g tissue-1, 39.8 +/- 0.7 mg X 100 mg protein-1) was significantly less than that in forced-trained rats (P less than 0.05). These results suggest that voluntary, mild exercise training may be more effective in the reduction of collagen accumulation in the aorta associated with the suppression of blood pressure increase than forced, vigorous exercise training in SHR.     

Contractile and biochemical properties of diaphragm: effects of exercise training and fatigue

The effect of high-intensity trained (6 X 4.5 min at 40 m/min, 15% grade, 2.5-min rest between bouts, 5 days/wk, for 6 wk) on contractile, biochemical, and fatigue properties of the rat diaphragm were examined. The exercise program produced significant elevations in the mitochondrial marker enzyme citrate synthase (mumol X g-1 X min-1) in the soleus (SOL) (27.2 +/- 1.5 vs. 46.7 +/- 2.4; mean +/- SE), deep vastus lateralis (DVL) (40.8 +/- 2.6 vs. 58.3 +/- 2.8), and superficial vastus lateralis (SVL) (8.5 +/- 0.6 vs. 11.4 +/- 0.7). No significant differences were observed in the crural (CRU) (45.9 +/- 2.0 vs. 44.0 +/- 2.3) or ventral costal (VEN) (41.5 +/- 2.0 vs. 45.8 +/- 2.6) diaphragmatic regions. Phosphofructokinase, the rate-limiting enzyme of glycolysis, significantly increased in the SOL (19.0 +/- 0.8 vs. 23.3 +/- 1.3 mumol X g-1 X min-1) and DVL (69.3 +/- 6.0 vs. 86.6 +/- 5.0), but no alterations were seen in the SVL (98.6 +/- 5.7 vs. 106.1 +/- 9.0), CRU (54.4 +/- 2.8 vs. 53.8 +/- 1.5), or VEN (44.7 +/- 2.4 vs. 46.4 +/- 1.4) posttraining. Diaphragm contractile properties, with the exception of an increased rate of fall in twitch tension, remained unchanged after training. Glycogen values were significantly higher in trained diaphragms at rest (6.54 +/- 0.39 vs. 4.86 +/- 0.41 mg/g) and during 1, 5, and 10 min of fatiguing stimulation. During fatigue no differences were observed in force, rate of rise in force, rate of fall in force, muscle lactate, ATP, or creatine phosphate in trained vs. control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endurance-training-induced cellular adaptations in respiratory muscles

Controversy exists concerning the adaptability of mammalian respiratory muscles in response to endurance training. We examined the effects of 8 wk of progressive treadmill exercise (45 min/day 5 days/wk) on the biochemical adaptations of rat diaphragm and intercostal muscles. Female Sprague-Dawley rats were randomly assigned to a sedentary control (n = 10) or an exercise-training group (n = 10). Endurance training resulted in an enhanced oxidative capacity in the anterior costal diaphragm as evidenced by a 29% increase (P less than 0.05) in the activity of succinate dehydrogenase (SDH) in trained animals compared with controls (4.15 +/- 0.13 vs. 3.21 +/- 0.17 mumol.g-1.min-1). Similarly, SDH activity in the intercostal muscles was 32% greater (P less than 0.05) in the trained animals than in the untrained animals (1.72 +/- 0.11 vs. 1.30 +/- 0.06 mumol.g-1.min-1). In contrast, the crural region of the diaphragm showed no significant increase (P greater than 0.05) in oxidative capacity as a result of the training program (3.28 +/- 0.12 vs. 3.13 +/- 0.18). Furthermore, training did not alter (P less than 0.05) lactate dehydrogenase activity in the intercostals or in the crural or the costal diaphragm. These data demonstrate that the oxidative capacity of the costal diaphragm and the intercostal muscles can be enhanced by increasing respiratory loads via regular endurance exercise. We speculate that the lack of metabolic adaptation in the crural region of the diaphragm was not due to limited plasticity of the fibers in this area but to failure to the exercise-training program to provide the appropriate stimulus for cellular adaptation.