Differential control of forearm and calf vascular resistance during one-leg exercise

The purpose of this study was to determine whether blood flow (BF) and vascular resistance (VR) are controlled differently in the nonactive arm and leg during submaximal rhythmic exercise. In eight healthy men we simultaneously measured BF to the forearm and calf (venous occlusion plethysmography) and arterial blood pressure (sphygmomanometry) and calculated whole limb VR before (control) and during 3 min of cycling with the contralateral leg at 38, 56, and 75% of peak one-leg O2 uptake (VO2). During the initial phase of exercise (0-1.5 min) at all work loads, BF increased and VR decreased in the forearm (P less than 0.05), whereas calf BF and VR remained at control levels. Thereafter, BF decreased and VR increased in parallel and progressive fashion in both limbs. At end exercise, forearm BF and VR were not different from control values (P greater than 0.05); however, in the calf, BF tended to be lower (P less than 0.05 at 75% peak VO2 only) and VR was higher (23 +/- 9, 44 +/- 14, and 88 +/- 23% above control at 38, 56, and 75% of peak VO2, respectively, all P less than 0.05). In a second series of studies, forearm and calf skin blood flow (laser-Doppler velocimetry) and arterial pressure were measured during the same levels of exercise in six of the subjects. Compared with control, skin BF was unchanged and VR was increased (P less than 0.05) in the forearm by end exercise at all work loads, whereas calf skin BF increased (P less than 0.05) and VR decreased (P less than 0.05). The present findings indicate that skeletal muscle and skin VR are controlled differently in the nonactive forearm and calf during the initial phase of rhythmic exercise with the contralateral leg. Skeletal muscle vasodilation occurs in the forearm but not in the calf; forearm skin vasoconstricts, whereas calf skin vasodilates. Finally, during exercise a time-dependent vasoconstriction occurs in the skeletal muscle of both limbs.     

Passive triceps surae stretch inhibits vasoconstriction in the nonexercised limb during posthandgrip muscle ischemia.

We investigated whether selective muscle mechanoreceptor activation in the lower limb opposes arm muscle metaboreceptor activation-mediated limb vasoconstriction. Seven subjects completed two trials: one control trial and one stretch trial. Both trials included 2 min of handgrip and 2 min of posthandgrip exercise muscle ischemia (PEMI). In the stretch trial, a 2-min sustained triceps surae stretch, by brief passive dorsiflexion of the right foot, was performed simultaneously during PEMI. Mean arterial pressure, heart rate, and forearm blood flow (FBF) in the nonexercised arm and forearm vascular conductance (FVC) in the nonexercised arm were measured. During PEMI in the control trial, mean arterial pressure was significantly greater and FBF and FVC were significantly lower than baseline values (P < 0.05 for each). In contrast, FBF and FVC during PEMI in the stretch trial exhibited different responses than in the control trial. FBF and FVC were significantly greater in the stretch trial than in the control trial (FBF, 5.5 +/- 0.4 vs. 3.8 +/- 0.4 ml x 100 ml(-1) x min(-1); FVC, 0.048 +/- 0.004 vs. 0.033 +/- 0.003 unit, respectively; P < 0.05). These results indicate that passive triceps surae stretch can inhibit vasoconstriction in the nonexercised forearm mediated via muscle metaboreceptor activation in the exercised arm.     

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin

We examined the effects of inhibiting nitric oxide synthase with Nomega-nitro-l-arginine-methyl ester (l-NAME) on total hindlimb blood flow, muscle microvascular recruitment, and hindlimb glucose uptake during euglycemic hyperinsulinemia in vivo in the rat. We used two independent methods to measure microvascular perfusion. In one group of animals, microvascular recruitment was measured using the metabolism of exogenously infused 1-methylxanthine (1-MX), and in a second group contrast-enhanced ultrasound (CEU) was used. Limb glucose uptake was measured by arterial-venous concentration differences after 2 h of insulin infusion. Saline alone did not alter femoral artery flow, glucose uptake, or 1-MX metabolism. Insulin (10 mU.min-1.kg-1) significantly increased hindlimb total blood flow (0.69 +/- 0.02 to 1.22 +/- 0.11 ml/min, P < 0.05), glucose uptake (0.27 +/- 0.05 to 0.95 +/- 0.08 micromol/min, P < 0.05), 1-MX uptake (5.0 +/- 0.5 to 8.5 +/- 1.0 nmol/min, P < 0.05), and skeletal muscle microvascular volume measured by CEU (10.0 +/- 1.6 to 15.0 +/- 1.2 video intensity units, P < 0.05). Addition of l-NAME to insulin completely blocked the effect of insulin on both total limb flow and microvascular recruitment (measured using either 1-MX or CEU) and blunted glucose uptake by 40% (P < 0.05). We conclude that insulin specifically recruits flow to the microvasculture in skeletal muscle via a nitric oxide-dependent pathway and that this may be important to insulin's overall action to regulate glucose disposal.     

Cutaneous laser-Doppler flowmetry: influence of underlying muscle blood flow

To find whether the measurement of skin blood flow (SkBF) by laser-Doppler flowmetry (LDF) is influenced by blood flow to underlying skeletal muscle, five subjects performed mild forearm exercise to induce a metabolic hyperemia in muscle in both forearms. This exercise consisted of alternative opening and closing of both hands at a frequency of approximately 1/s for a duration of 3 min. This exercise was performed twice by each subject. Forearm blood flow (FBF) by plethysmography increased from 2.64 +/- 0.49 (rest) to 31.11 +/- 9.95 ml.100 ml-1.min-1 (immediately after exercise) (P less than 0.001). No statistically significant postexercise increase was observed in LDF measured on the dorsal (110 +/- 21 to 105 +/- 21 mV) or ventral surface (266 +/- 113 to 246 +/- 77 mV) of the forearm. LDF measured from the chest also showed no significant change, indicating that the exercise was too mild to have reflex effects on SkBF. Moreover, the slope of the logarithmic linear regression and the half-time for recovery during the postexercise period for FBF were not reflected in LDF measurements from any of the three sites. We conclude that LDF measured from the skin surface is not influenced by blood flow to underlying skeletal muscle.     

Do P2X purinergic receptors regulate skeletal muscle blood flow during exercise?

Although there is evidence that sympathetic nerves release ATP as a neurotransmitter to produce vasoconstriction via P2X purinergic receptors, the role of these receptors in the regulation of blood flow to exercising skeletal muscle has yet to be determined. We hypothesized that there is tonic P2X receptor-mediated vasoconstriction in exercising skeletal muscle. To test this hypothesis, the effect of P2X receptor blockade on skeletal muscle blood flow was examined in six exercising mongrel dogs. P2X receptor antagonism was accomplished with pyridoxal-phosphate-6-azophenyl-2'4'-disulfonic acid (PPADs). Animals were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. PPADs (40 mg) was infused as a bolus into the femoral artery catheter during steady-state exercise at 6 miles/h. Intra-arterial infusion of PPADs increased iliac blood flow from 542 +/- 55 to 677 +/- 69 ml/min (P < 0.05) and iliac vascular conductance from 5.17 +/- 0.62 to 6.53 +/- 0.80 ml.min(-1).mmHg(-1). The PPADs infusion did not affect blood flow in the contralateral iliac artery. These data support the hypothesis that P2X purinergic receptors produce vasoconstriction in exercising skeletal muscle.     

Metabolic forearm vasodilation is enhanced following Bier block with phentolamine

The extent to which sympathetic nerve activity restrains metabolic vasodilation in skeletal muscle remains unclear. We determined forearm blood flow (FBF; ultrasound/Doppler) and vascular conductance (FVC) responses to 10 min of ischemia [reactive hyperemic blood flow (RHBF)] and 10 min of systemic hypoxia (inspired O(2) fraction = 0.1) before and after regional sympathetic blockade with the alpha-receptor antagonist phentolamine via Bier block in healthy humans. In a control group, we performed sham Bier block with saline. Consistent with alpha- receptor inhibition, post-phentolamine, basal FVC (FBF/mean arterial pressure) increased (pre vs. post: 0.42 +/- 0.05 vs. 1.03 +/- 0.21 units; P < 0.01; n = 12) but did not change in the saline controls (pre vs. post: 0.56 +/- 0.14 vs. 0.53 +/- 0.08 units; P = not significant; n = 5). Post-phentolamine, total RHBF (over 3 min) increased substantially (pre vs. post: 628 +/- 75 vs. 826 +/- 92 ml/min; P < 0.01) but did not change in the controls (pre vs. post: 618 +/- 66 vs. 661 +/- 35 ml/min; P = not significant). In all conditions, compared with peak RHBF, peak skin reactive hyperemia was markedly delayed. Furthermore, post-phentolamine (pre vs. post: 0.43 +/- 0.06 vs. 1.16 +/- 0.17 units; P < 0.01; n = 8) but not post-saline (pre vs. post: 0.93 +/- 0.16 vs. 0.87 +/- 0.19 ml/min; P = not significant; n = 5), the FVC response to hypoxia (arterial O(2) saturation = 77 +/- 1%) was markedly enhanced. These data suggest that sympathetic vasoconstrictor nerve activity markedly restrains skeletal muscle vasodilation induced by local (forearm ischemia) and systemic (hypoxia) vasodilator stimuli.     

Local vasodilatation with metacholine, but not with nitroprusside, increases forearm glucose uptake

Insulin is known to increase blood flow in parallel to glucose uptake in skeletal muscle. However, it is not known if an increase in blood flow by itself is associated with an increase in glucose uptake in the absence of hyperinsulinemia. To investigate further this matter, the effect of increased blood flow on forearm glucose uptake was studied in the fasting state during intra-arterial infusions of two different vasodilators, metacholine and nitroprusside, in 19 hypertensive subjects. Both metacholine (4 microg/min) and nitroprusside (10 microg/min) increased resting forearm blood flow, measured by venous occlusion plethysmography, to a similar degree (180 % and 170 %, respectively, p<0.0001 for both). However, metacholine infusion increased the forearm glucose uptake from 2.0+/-0.9 (S.D.) during rest to 5.5+/-3.0 umol/min/100 ml tissue (p<0.0001), while no significant change in glucose uptake was seen during nitroprusside infusion (2.3+/-1.4 micromol/min/100 ml tissue). In conclusion, vasodilatation induced by metacholine, but not by nitroprusside, increased glucose uptake in the forearm of hypertensive patients. Thus, an increase in forearm blood flow does not necessarily improve glucose uptake in the forearm during the fasting state.     

Effect of heat stress on muscle blood flow during dynamic handgrip exercise

During exercise in a hot environment, blood flow in the exercising muscles may be reduced in favour of the cutaneous circulation. The aim of our study was to examine whether an acute heat exposure (65-70 degrees C) in sauna conditions reduces the blood flow in forearm muscles during handgrip exercise in comparison to tests at thermoneutrality (25 degrees C). Nine healthy men performed dynamic handgrip exercise of the right hand by rhythmically squeezing a water-filled rubber tube at 13% (light), and at 34% (moderate) of maximal voluntary contraction. The left arm served as a control. The muscle blood flow was estimated as the difference in plethysmographic blood flow between the exercising and the control forearm. Skin blood flow was estimated by laser Doppler flowmetry in both forearms. Oesophageal temperature averaged 36.92 (SEM 0.08) degrees C at thermoneutrality, and 37.74 (SEM 0.07) degrees C (P less than 0.01) at the end of the heat stress. The corresponding values for heart rate were 58 (SEM 2) and 99 (SEM 5) beats.min-1 (P less than 0.01), respectively. At 25 degrees C, handgrip exercise increased blood flow in the exercising forearm above the control forearm by 6.0 (SEM 0.8) ml.100 ml-1.min-1 during light exercise, and by 17.9 (SEM 2.5) ml.100 ml-1.min-1 during moderate exercise. In the heat, the increases were significantly higher: 12.5 (SEM 2.2) ml.100 ml-1.min-1 at the light exercise level (P less than 0.01), and 32.2 (SEM 5.9) ml.100 ml-1.min-1 (P less than 0.05) at the moderate exercise level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of vasodilator potency of adrenomedulling and proadrenomedullin N-terminal 20 peptide in human

Adrenomedullin (ADM) and proadrenomedullin N-terminal peptide (PAMP), both of which are derived from preproadrenomedullin, are reported to have a potent hypotensive effect in animals. However, no data are available concerning the vasodilatory potency of PAMP or comparing this potency to that of ADM in human vasculature. We examined the effects of intra-arterial infusion of graded doses of ADM (1.25, 2.5, 5.0 and 7.5 pmol/min per 100 ml of tissue) and PAMP (125, 250, 500, 750 and 1000 pmol/min per 100 ml of tissue) on total forearm blood flow and forearm skin blood flow in 11 healthy subjects. ADM increased total forearm blood flow from 2.9 +/- 0.4 to 8.6 +/- 1.1 ml/min per 100 ml (p < 0.01), and skin blood flow from 0.07 +/- 0.02 to 0.14 +/- 0.03 volts (p < 0.01). In contrast to this potent vasodilatory effect, a significant rise in forearm skeletal blood flow was seen only in response to the maximum dose of PAMP (from 2.7 +/- 0.5 to 5.3 +/- 1.0 ml/min per 100 ml; p < 0.01). In addition, PAMP had no significant vasoactive effect on skin blood flow (from 0.06 +/- 0.02 to 0.09 +/- 0.03 volts; NS). In conclusion, the skeletal muscle vasodilator potency of PAMP is less than one hundredth of that of ADM in human forearm. Given its weak dilator potency, it seems unlikely that PAMP alone could significantly regulate resistance vessel tone as a circulating hormone in humans.     

Noninvasive monitoring of deterioration in skeletal muscle function with forearm cast immobilization and the prevention of deterioration

BACKGROUND: In this research inactivity was simulated by immobilizing the forearm region in a plaster cast. Changes in skeletal muscle oxidative function were measured using near-infrared spectroscopy (NIRS), and the preventative effect of the training protocol on deterioration of skeletal muscle and the clinical utility of NIRS were examined. METHODS: Fourteen healthy adult men underwent immobilization of the forearm of the non-dominant arm by plaster cast for 21 days. Eight healthy adult subjects were designated as the immobilization group (IMM) and six were designated as the immobilization + training group (IMM+TRN). Grip strength, forearm circumference and dynamic handgrip exercise endurance were measured before and after the 21-day immobilization period. Using NIRS, changes in oxidative function of skeletal muscles were also evaluated. Muscle oxygen consumption recovery was recorded after the completion of 60 seconds of 40% maximum voluntary contraction (MVC) dynamic handgrip exercise 1 repetition per 4 seconds and the recovery time constant (TcVO2mus) was calculated. RESULTS: TcVO2mus for the IMM was 59.7 +/- 5.5 seconds (average +/- standard error) before immobilization and lengthened significantly to 70.4 +/- 5.4 seconds after immobilization (p < 0.05). For the IMM+TRN, TcVO2mus was 78.3 +/- 6.2 seconds before immobilization and training and shortened significantly to 63.1 +/- 5.6 seconds after immobilization and training (p < 0.05). CONCLUSIONS: The training program used in this experiment was effective in preventing declines in muscle oxidative function and endurance due to immobilization. The experimental results suggest that non-invasive monitoring of skeletal muscle function by NIRS would be possible in a clinical setting.     

Previous exercise attenuates muscle sympathetic activity and increases blood flow during acute euglycemic hyperinsulinemia.

Insulin infusion causes muscle vasodilation, despite the increase in sympathetic nerve activity. In contrast, a single bout of exercise decreases sympathetic activity and increases muscle blood flow during the postexercise period. We tested the hypothesis that muscle sympathetic activity would be lower and muscle vasodilation would be higher during hyperinsulinemia performed after a single bout of dynamic exercise. Twenty-one healthy young men randomly underwent two hyperinsulinemic euglycemic clamps performed after 45 min of seated rest (control) or bicycle exercise (50% of peak oxygen uptake). Muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow (FBF, plethysmography), blood pressure (BP, oscillometric method), and heart rate (HR, ECG) were measured at baseline (90 min after exercise or seated rest) and during hyperinsulinemic euglycemic clamps. Baseline glucose and insulin concentrations were similar in the exercise and control sessions. Insulin sensitivity was unchanged by previous exercise. During the clamp, insulin levels increased similarly in both sessions. As expected, insulin infusion increased MSNA, FBF, BP, and HR in both sessions (23 +/- 1 vs. 36 +/- 2 bursts/min, 1.8 +/- 0.1 vs. 2.2 +/- 0.2 ml.min(-1).100 ml(-1), 89 +/- 2 vs. 92 +/- 2 mmHg, and 58 +/- 1 vs. 62 +/- 1 beats/min, respectively, P < 0.05). BP and HR were similar between sessions. However, MSNA was significantly lower (27 +/- 2 vs. 31 +/- 2 bursts/min), and FBF was significantly higher (2.2 +/- 0.2 vs. 1.8 +/- 0.1 ml.min(-1).100 ml(-1), P < 0.05) in the exercise session compared with the control session. In conclusion, in healthy men, a prolonged bout of dynamic exercise decreases MSNA and increases FBF. These effects persist during acute hyperinsulinemia performed after exercise.     

Effect of fitness on arm vascular and metabolic responses to upper body exercise

We investigated arm perfusion and metabolism during upper body exercise. Eight average, fit subjects and seven rowers, mean +/- SE maximal oxygen uptake (VO2 max) 157 +/- 7 and 223 +/- 14 ml O2. kg(-0.73).min(-1), respectively, performed incremental arm cranking to exhaustion. Arm blood flow (ABF) was measured with thermodilution and arm muscle mass was estimated by dual-energy X-ray absorptiometry. During maximal arm cranking, pulmonary VO2 was approximately 45% higher in the rowers compared with the untrained subjects and peak ABF was 6.44 +/- 0.40 and 4.55 +/- 0.26 l/min, respectively (P < 0.05). The arm muscle mass for the rowers and the untrained subjects was 3.5 +/- 0.4 and 3.3 +/- 0.1 kg, i.e., arm perfusion was 1.9 +/- 0.2 and 1.4 +/- 0.1 l blood.kg(-1).min(-1), respectively (P < 0.05). The arteriovenous O2 difference was 156 +/- 7 and 120 +/- 8 ml/l, respectively, and arm VO2 was 0.98 +/- 0.08 and 0.60 +/- 0.04 l/min corresponding with 281 +/- 22 and 181 +/- 12 ml/kg, while arm O(2) diffusional conductance was 49.9 +/- 4.3 and 18.6 +/- 3.2 ml.min(-1).mmHg(-1), respectively (P < 0.05). Also, lactate release in the rowers was almost three times higher than in the untrained subjects (26.4 +/- 1.1 vs. 9.5 +/- 0.4 mmol/min, P < 0.05). The energy requirement of an approximately 50% larger arm work capacity after long-term arm endurance training is covered by an approximately 60% increase in aerobic metabolism and an almost tripling of the anaerobic capacity.     

Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise.

Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle training, 30 min/day, 6 days/wk for 10 wk at approximately 70% of maximal O(2) uptake) and untrained (UT) legs of healthy men (H) [n = 6, age 60 +/- 2 (SE) yr] and patients with Type 2 diabetes mellitus (DM) (n = 4, age 56 +/- 3 yr) during a hyperinsulinemic ( approximately 16,000 pmol/l), isoglycemic clamp with a final 30 min of superimposed two-legged exercise at 70% of individual maximal heart rate. With superimposed exercise, leg glucose extraction decreased (P < 0.05), and leg blood flow and leg glucose clearance increased (P < 0.05), compared with hyperinsulinemia alone. During exercise, leg blood flow was similar in both groups of subjects and between T and UT legs, whereas glucose extraction was always higher (P < 0.05) in T compared with UT legs (15.8 +/- 1.2 vs. 14.6 +/- 1.8 and 11.9 +/- 0.8 vs. 8.8 +/- 1.8% for H and DM, respectively) and leg glucose clearance was higher in T (H: 73 +/- 8, DM: 70 +/- 10 ml. min(-1). kg leg(-1)) compared with UT (H: 63 +/- 8, DM: 45 +/- 7 ml. min(-1). kg leg(-1)) but not different between groups (P > 0.05). From these results it can be concluded that, in both diabetic and healthy aged muscle, exercise adds to a maximally insulin-stimulated glucose clearance and that glucose extraction and clearance are both enhanced by training.     

Effect of aerobic and resistance exercise training on vascular function in heart failure

Exercise training of a muscle group improves local vascular function in subjects with chronic heart failure (CHF). We studied forearm resistance vessel function in 12 patients with CHF in response to an 8-wk exercise program, which specifically excluded forearm exercise, using a crossover design. Forearm blood flow (FBF) was measured using strain-gauge plethysmography. Responses to three dose levels of intra-arterial acetylcholine were significantly augmented after exercise training when analyzed in terms of absolute flows (7.0 +/- 1.8 to 10.9 +/- 2.1 ml x 100 ml(-1) x min(-1) for the highest dose, P < 0.05 by ANOVA), forearm vascular resistance (21.5 +/- 5.0 to 15.3 +/- 3.9 ml x 100 ml forearm(-1) x min(-1), P < 0.01), or FBF ratios (P < 0.01, ANOVA). FBF ratio responses to sodium nitroprusside were also significantly increased after training (P < 0.05, ANOVA). Reactive hyperemic flow significantly increased in both upper limbs after training (27.9 +/- 2.7 to 33.5 +/- 3.1 ml x 100 ml(-1) x min(-1), infused limb; P < 0.05 by paired t-test). Exercise training improves endothelium-dependent and -independent vascular function and peak vasodilator capacity in patients with CHF. These effects on the vasculature are generalized, as they were evident in a vascular bed not directly involved in the exercise stimulus.     

Effects of an oral glucose tolerance test on the myogenic response in healthy individuals

The myogenic response, the inherent ability of blood vessels to rapidly respond to changes in transmural pressure, is involved in local blood flow autoregulation. Animal studies suggest that both acute hyperglycemia and hyperinsulinemia may impair myogenic vasoconstriction. The purpose of this study was to examine the effects of an oral glucose load on brachial mean blood velocity (MBV) during increases in forearm transmural pressure in humans. Eight healthy men and women (38 +/- 5 yr) underwent an oral glucose tolerance test (OGTT). MBV (in cm/s; Doppler ultrasound) responses to a rise in forearm transmural pressure (arm tank suction, -50 mmHg) were studied before and every 30 min for 120 min during the OGTT. Before the start of the OGTT, MBV was lower than baseline values 30 and 60 s after the application of negative pressure. This suggests that myogenic constriction was present. During the OGTT, blood glucose rose from 88 +/- 2 to 120 +/- 6 mg/dl (P < 0.05) and insulin rose from 14 +/- 1 to 101 +/- 32 microU/ml (P < 0.05). Glucose loading attenuated the reduction in MBV with arm suction (Delta-0.73 +/- 0.14 vs. Delta-1.67 +/- 0.43 cm/s and Delta-1.07 +/- 0.14 vs. Delta-2.38 +/- 0.54 cm/s, respectively, during 30 and 60 s of suction postglucose compared with preglucose values; all P < 0.05). We observed no such time effect for myogenic responses during a sham OGTT. In an additional 5 subjects, glucose loading had no effect on brachial diameters with the application of negative pressure. Oral glucose loading leads to attenuated myogenic vasoconstriction in healthy individuals. The role that this diminished postglucose reactivity plays in mediating postprandial hypotension and/or orthostasis needs to be further explored.     

Prior exercise and postprandial substrate extraction across the human leg

Prior exercise decreases postprandial plasma triacylglycerol (TG) concentrations, possibly through changes to skeletal muscle TG extraction. We measured postprandial substrate extraction across the leg in eight normolipidemic men aged 21-46 yr. On the afternoon preceding one trial, subjects ran for 2 h at 64 +/- 1% of maximal oxygen uptake (exercise); before the control trial, subjects had refrained from exercise. Samples of femoral arterial and venous blood were obtained, and leg blood flow was measured in the fasting state and for 6 h after a meal (1.2 g fat, 1.2 g carbohydrate/kg body mass). Prior exercise increased time averaged postprandial TG clearance across the leg (total TG: control, 0.079 +/- 0.014 ml.100 ml tissue(-1).min(-1) ; exercise, 0.158 +/- 0.023 ml.100 ml tissue(-1).min(-1), P <0.01), particularly in the chylomicron fraction, so that absolute TG uptake was maintained despite lower plasma TG concentrations (control, 1.53 +/- 0.13 mmol/l; exercise, 1.01 +/- 0.16 mmol/l, P < 0.001). Prior exercise increased postprandial leg blood flow and glucose uptake (both P < 0.05). Mechanisms other than increased leg TG uptake must account for the effect of prior exercise on postprandial lipemia.     

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.     

Estimations of muscle interstitial insulin, glucose, and lactate in type 2 diabetic subjects

Previous measurement of insulin in human muscle has shown that interstitial muscle insulin and glucose concentrations are approximately 30-50% lower than in plasma during hyperinsulinemia in normal subjects. The aims of this study were to measure interstitial muscle insulin and glucose in patients with type 2 diabetes to evaluate whether transcapillary transport is part of the peripheral insulin resistance. Ten patients with type 2 diabetes and ten healthy controls matched for sex, age, and body mass index were investigated. Plasma and interstitial insulin, glucose, and lactate (measured by intramuscular in situ-calibrated microdialysis) in the medial quadriceps femoris muscle were analyzed during a hyperinsulinemic euglycemic clamp. Blood flow in the contralateral calf was measured by vein plethysmography. At steady-state clamping, at 60-120 min, the interstitial insulin concentration was significantly lower than arterial insulin in both groups (409 +/- 86 vs. 1,071 +/- 99 pmol/l, P < 0.05, in controls and 584 +/- 165 vs. 1, 253 +/- 82 pmol/l, P < 0.05, in diabetic subjects, respectively). Interstitial insulin concentrations did not differ significantly between diabetic subjects and controls. Leg blood flow was significantly higher in controls (8.1 +/- 1.2 vs. 4.4 +/- 0.7 ml. 100 g(-1).min(-1) in diabetics, P < 0.05). Calculated glucose uptake was less in diabetic patients compared with controls (7.0 +/- 1.2 vs. 10.8 +/- 1.2 micromol. 100 g(-1).min(-1), P < 0.05, respectively). Arterial and interstitial lactate concentrations were both higher in the control group (1.7 +/- 0.1 vs. 1.2 +/- 0.1, P < 0. 01, and 1.8 +/- 0.1 vs. 1.2 +/- 0.2 mmol/l, P < 0.05, in controls and diabetics, respectively). We conclude that, during hyperinsulinemia, muscle interstitial insulin and glucose concentrations did not differ between patients with type 2 diabetes and healthy controls despite a significantly lower leg blood flow in diabetic subjects. It is suggested that decreased glucose uptake in type 2 diabetes is caused by insulin resistance at the cellular level rather than by a deficient access of insulin and glucose surrounding the muscle cell.     

Metformin increases blood flow and forearm glucose uptake in a group of non-obese type 2 diabetes patients.

The present study was designed to determine the effects of metformin on the forearm glucose uptake and blood flow after an oral glucose challenge. Eleven normal subjects, and ten non-obese type 2 diabetes patients without medication of anti-hyperglycemic drug and with medication of metformin for four weeks, were studied after an overnight fast (12-14 h) and 3 hours after ingestion of 75 g of glucose. Peripheral glucose metabolism was analyzed by the forearm technique combined with indirect calorimetry. The forearm glucose uptake increased in diabetes patients taking metformin (63.5+/-9.1 VS. 39.1+/-5.3 mg/100 ml FA. 3 h). The increase of forearm glucose uptake was due to increase of blood flow. The glucose oxidation was greater in the group treated with metformin, compared to the same group without anti-hyperglycemic drug (19.3+/-2.6 VS. 7.7+/-2.6 mg/100 ml FA. 3 hrs). The free fatty acids were higher in diabetes patients, which normalized after taking metformin. In conclusion, it was found that in these participants metformin acts in insulin resistance; it increases glucose muscle uptake and blood flow. The enhancement of blood flow and lower free fatty acids, not described yet, could be direct effects of the drug or due to reduced glucose toxicity. These positive effects must be responsible for the improvement in vascular function.     

Differential effects of aging on limb blood flow in humans

Aging appears to attenuate leg blood flow during exercise; in contrast, such data are scant and do not support this contention in the arm. Therefore, to determine whether aging has differing effects on blood flow in the arm and leg, eight young (22 +/- 6 yr) and six old (71 +/- 15 yr) subjects separately performed dynamic knee extensor [0, 3, 6, 9 W; 20, 40, 60% maximal work rate (WRmax)] and handgrip exercise (3, 6, 9 kg at 0.5 Hz; 20, 40, 60% WRmax). Arterial diameter, blood velocity (Doppler ultrasound), and arterial blood pressure (radial tonometry) were measured simultaneously at each of the submaximal workloads. Quadriceps muscle mass was smaller in the old (1.6 +/- 0.1 kg) than the young (2.1 +/- 0.2 kg). When normalized for this difference in muscle mass, resting seated blood flow was similar in young and old subjects (young, 115 +/- 28; old, 114 +/- 39 ml x g(-1) x min(-1)). During exercise, blood flow and vascular conductance were attenuated in the old whether expressed in absolute terms for a given absolute workload or more appropriately expressed as blood flow per unit muscle mass at a given relative exercise intensity (young, 1,523 +/- 329; old, 1,340 +/- 157 ml x kg(-1) x min(-1) at 40% WRmax). In contrast, aging did not affect forearm muscle mass or attenuate rest or exercise blood flow or vascular conductance in the arm. In conclusion, aging induces limb-specific alterations in exercise blood flow regulation. These alterations result in reductions in leg blood flow during exercise but do not impact forearm blood flow.