Effects of a prior high-intensity knee-extension exercise on muscle recruitment and energy cost: a combined local and global investigation in humans

The effects of a priming exercise bout on both muscle energy production and the pattern of muscle fibre recruitment during a subsequent exercise bout are poorly understood. The purpose of the present study was to determine whether a prior exercise bout which is known to increase O₂ supply and to induce a residual acidosis could alter energy cost and muscle fibre recruitment during a subsequent heavy-intensity knee-extension exercise. Fifteen healthy subjects performed two 6 min bouts of heavy exercise separated by a 6 min resting period. Rates of oxidative and anaerobic ATP production, determined with ³¹P-magnetic resonance spectroscopy, and breath-by-breath measurements of pulmonary oxygen uptake were obtained simultaneously. Changes in muscle oxygenation and muscle fibre recruitment occurring within the quadriceps were measured using near-infrared spectroscopy and surface electromyography. The priming heavy-intensity exercise increased motor unit recruitment ( P < 0.05) in the early part of the subsequent exercise bout but did not alter muscle energy cost. We also observed a reduced deoxygenation time delay, whereas the deoxygenation amplitude was increased ( P < 0.01). These changes were associated with an increased oxidative ATP cost after ∼50 s ( P < 0.05) and a slight reduction in the overall anaerobic rate of ATP production (0.11 ± 0.04 m m min⁻¹ W⁻¹ for bout 1 and 0.06 ± 0.11 m m min⁻¹ W⁻¹ for bout 2; P < 0.05). We showed that a priming bout of heavy exercise led to an increased recruitment of motor units in the early part of the second bout of heavy exercise. Considering the increased oxidative cost and the unaltered energy cost, one could suggest that our results illustrate a reduced metabolic strain per fibre.     

Effect of dexamethasone on skeletal muscle Na+,K+ pump subunit specific expression and K+ homeostasis during exercise in humans

The effect of dexamethasone on Na⁺,K⁺ pump subunit expression and muscle exchange of K⁺ during exercise in humans was investigated. Nine healthy male subjects completed a randomized double blind placebo controlled protocol, with ingestion of dexamethasone (Dex: 2 × 2 mg per day) or placebo (Pla) for 5 days. Na⁺,K⁺ pump catalytic α1 and α2 subunit expression was ∼17% higher ( P < 0.05) and the structural β1 and β2 subunit expression was ∼6–8% higher ( P < 0.05) after Dex compared with Pla. During one-legged knee-extension for 10 min at low intensity (LI; 18.6 ± 1.0 W), two moderate intensity (51.7 ± 2.4 W) exercise bouts (MI₁: 5 min; 2 min recovery; MI₂: exhaustive) and two high-intensity (71.7 ± 2.5 W) exercise bouts (HI₁: 1 min 40 s; 2 min recovery; HI₂: exhaustive), femoral venous K⁺ was lower ( P < 0.05) in Dex compared with Pla. Thigh K⁺ release was lower ( P < 0.05) in Dex compared with Pla in LI and MI, but not in HI. Time to exhaustion in MI₂ tended to improve (393 ± 50 s versus 294 ± 41 s; P = 0.07) in Dex compared with Pla, whereas no difference was detected in HI₂ (106 ± 10 s versus 108 ± 9 s). The results indicate that an increased Na⁺,K⁺ pump expression per se is of importance for thigh K⁺ reuptake at the onset of low and moderate intensity exercise, but less important during high intensity exercise.     

Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow was quantified by near infrared spectroscopy and indocyanine green in six healthy humans during dynamic knee extension exercise with and without combined pharmacological inhibition of NO synthase (NOS) and PG by l -NAME and indomethacin, respectively. Microdialysis was applied to determine interstitial release of PG. Compared to control, combined blockade resulted in a 5- to 10-fold lower muscle interstitial PG level. During control incremental knee extension exercise, mean blood flow in the quadriceps muscles rose from 10 ± 0.8 ml (100 ml tissue)⁻¹ min⁻¹ at rest to 124 ± 19, 245 ± 24, 329 ± 24 and 312 ± 25 ml (100 ml tissue)⁻¹ min⁻¹ at 15, 30, 45 and 60 W, respectively. During inhibition of NOS and PG, blood flow was reduced to 8 ± 0.5 ml (100 ml tissue)⁻¹ min⁻¹ at rest, and 100 ± 13, 163 ± 21, 217 ± 23 and 256 ± 28 ml (100 ml tissue)⁻¹ min⁻¹ at 15, 30, 45 and 60 W, respectively ( P < 0.05 vs. control). In conclusion, combined inhibition of NOS and PG reduced muscle blood flow during dynamic exercise in humans. These findings demonstrate an important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular contraction.     

Cardiac and vasomotor components of the carotid baroreflex control of arterial blood pressure during isometric exercise in humans

We sought to examine the importance of the cardiac component of the carotid baroreflex (CBR) in control of blood pressure during isometric exercise. Nine subjects performed 4 min of ischaemic isometric calf exercise at 20% of maximum voluntary contraction. Trials were repeated with β₁-adrenergic blockade (metoprolol, 0.15 ± 0.003 mg kg⁻¹) or parasympathetic blockade (glycopyrrolate, 13.6 ± 1.5 μg kg⁻¹). CBR function was determined using rapid pulses of neck pressure and neck suction from +40 to −80 mmHg, while heart rate (HR), mean arterial pressure (MAP) and changes in stroke volume (SV, Modelflow method) were measured. Metoprolol decreased and glycopyrrolate increased HR and cardiac output both at rest and during exercise ( P < 0.05), while resting and exercising blood pressure were unchanged. Glycopyrrolate reduced the maximal gain ( G _max) of the CBR-HR function curve (−0.58 ± 0.10 to −0.06 ± 0.01 beats min⁻¹ mmHg⁻¹, P < 0.05), but had no effect on the G _max of the CBR-MAP function curve. During isometric exercise the CBR-HR curve was shifted upward and rightward in the metoprolol and no drug conditions, while the control of HR was significantly attenuated with glycopyrrolate ( P < 0.05). Regardless of drug administration isometric exercise produced an upward and rightward resetting of the CBR control of MAP with no change in G _max. Thus, despite marked reductions in CBR control of HR following parasympathetic blockade, CBR control of blood pressure was well maintained. These data suggest that alterations in vasomotor tone are the primary mechanism by which the CBR modulates blood pressure during low intensity isometric exercise.     

Fluid replacement and heat stress during exercise alter post-exercise cardiac haemodynamics in endurance exercise-trained men

It has been reported that endurance exercise-trained men have decreases in cardiac output with no change in systemic vascular conductance during post-exercise hypotension, which differs from sedentary and normally active populations. As inadequate hydration may explain these differences, we tested the hypothesis that fluid replacement prevents this post-exercise fall in cardiac output, and further, exercise in a warm environment would cause greater decreases in cardiac output. We studied 14 trained men (     4.66 ± 0.62 l min⁻¹) before and to 90 min after cycling at 60%     for 60 min under three conditions: Control (no water was consumed during exercise in a thermoneutral environment), Fluid (water was consumed to match sweat loss during exercise in a thermoneutral environment) and Warm (no water was consumed during exercise in a warm environment). Arterial pressure and cardiac output were measured pre- and post-exercise in a thermoneutral environment. The fall in mean arterial pressure following exercise was not different between conditions ( P = 0.453). Higher post-exercise cardiac output (Δ 0.41 ± 0.17 l min⁻¹; P = 0.027), systemic vascular conductance (Δ 6.0 ± 2.2 ml min⁻¹ mmHg⁻¹ ; P = 0.001) and stroke volume (Δ 9.1 ± 2.1 ml beat⁻¹; P < 0.001) were seen in Fluid compared to Control, but there was no difference between Fluid and Warm (all P > 0.05). These data suggest that fluid replacement mitigates the post-exercise decrease in cardiac output in endurance-exercise trained men. Surprisingly, exercise in a warm environment also mitigates the post-exercise fall in cardiac output.     

Cytochrome P450 2C9 plays an important role in the regulation of exercise-induced skeletal muscle blood flow and oxygen uptake in humans

Previous studies show that exercise-induced hyperaemia is unaffected by systemic inhibition of nitric oxide synthase (NOS) and it has been proposed that this may be due to compensation by other vasodilators. We studied the involvement of cytochrome P450 2C9 (CYP 2C9) in the regulation of skeletal muscle blood flow in humans and the interaction between CYP 2C9 and NOS. Seven males performed knee extensor exercise. Blood flow was measured by thermodilution and blood samples were drawn frequently from the femoral artery and vein at rest, during exercise and in recovery. The protocol was repeated three times on the same day. The first and the third protocols were controls, and in the second protocol either the CYP 2C9 inhibitor sulfaphenazole alone, or sulfaphenazole in combination with the NOS inhibitor N ^ω-monomethyl- l -arginine ( l -NMMA) were infused. Compared with control there was no difference in blood flow at any time with sulfaphenazole infusion (   P > 0.05  ) whereas with infusion of sulfaphenazole and l -NMMA, blood flow during exercise was 16 ± 4 % lower than in control (9 min: 3.67 ± 0.31 vs. 4.29 ± 0.20 l min⁻¹;   P < 0.05  ). Oxygen uptake during exercise was 12 ± 3 % lower (9 min: 525 ± 46 vs. 594 ± 24 ml min⁻¹;   P < 0.05  ) with co-infusion of sulfaphenazole and l -NMMA, whereas oxygen uptake during sulfaphenazole infusion alone was not different from that of control (   P > 0.05  ). The results demonstrate that CYP 2C9 plays an important role in the regulation of hyperaemia and oxygen uptake during exercise. Since inhibition of neither NOS nor CYP 2C9 alone affect skeletal muscle blood flow, an interaction between CYP 2C9 and NOS appears to exist so that a CYP-dependent vasodilator mechanism takes over when NO production is compromised.     

A respiratory response to the activation of the muscle metaboreflex during concurrent hypercapnia in man

In this study, we aimed to assess the ventilatory and cardiovascular responses to the combined activation of the muscle metaboreflex and the ventilatory chemoreflex, achieved by postexercise circulatory occlusion (PECO) and euoxic hypercapnia (end-tidal partial pressure of CO₂ 7 mmHg above normal), respectively. Eleven healthy subjects (4 women and 7 men; 29 ± 4.4 years old; mean ± s.d. ) undertook the following four trials, in random order: 2 min of isometric handgrip exercise followed by 2 min of PECO with hypercapnia; 2 min of isometric handgrip exercise followed by 2 min of PECO while breathing room air; 4 min of rest with hypercapnia; and 4 min of rest while breathing room air. Ventilation was significantly increased during exercise in both the hypercapnic (+3.17 ± 0.82 l min⁻¹) and the room air breathing trials (+2.90 ± 0.26 l min⁻¹; all P < 0.05). During PECO, ventilation returned to pre-exercise levels when breathing room air (+0.52 ± 0.37 l min⁻¹; P > 0.05), but it remained elevated during hypercapnia (+3.77 ± 0.23 l min⁻¹; P < 0.05). The results indicate that the muscle metaboreflex stimulates ventilation with concurrent chemoreflex activation. These findings have implications for disease states where effort intolerance and breathlessness are linked.     

Fetal cerebral blood flow, electrocorticographic activity, and oxygenation: responses to acute hypoxia

Arterial blood gases are critical in regulation of cerebral blood flow (CBF) and cerebral metabolic rate for O₂ (CMRO₂). However, the relation of these variables to cortical tissue     (t     ), and electrocorticographic (ECoG) activity (high voltage low frequency, HVLF, versus low voltage high frequency, LVHF), are not well defined. In the fetus, we tested the hypothesis that ECoG pattern is associated closely with cerebral oxygenation. In fetal sheep ( n = 8) with laser Doppler flowmeter, fluorescent O₂ probe and ECoG electrodes, we measured laser Doppler CBF (LD-CBF), t     , ECoG and spectral edge frequency-90 (SEF₉₀) in response to 40 min isocapnic hypoxia. In the normoxic fetus, LD-CBF and CMRO₂ correlated highly with ECoG state. With a shift from HVLF to LVHF, t     decreased followed by increased LD-CBF (18%) and CMRO₂ (13%). With acute hypoxia (     = 12 ± 1 Torr), t     decreased to ∼3 Torr, LD-CBF increased 48 ± 10%, ECoG shifted to chiefly the HVLF state, SEF₉₀ decreased ∼15%, and CMRO₂ decreased ∼20% ( P < 0.05 for each). For the normoxic fetus, CBF was closely related to ECoG state, but this association was less evident during acute hypoxia. We speculate that, in the otherwise stressed fetus, acute hypoxia may further compromise cerebral oxygenation.     

Glucose clearance is higher in arm than leg muscle in type 2 diabetes

Insulin-mediated glucose clearance (GC) is diminished in type 2 diabetes. Skeletal muscle has been estimated to account for essentially all of the impairment. Such estimations were based on leg muscle and extrapolated to whole body muscle mass. However, skeletal muscle is not a uniform tissue and insulin resistance may not be evenly distributed. We measured basal and insulin-mediated (1 pmol min⁻¹ kg⁻¹) GC simultaneously in the arm and leg in type 2 diabetes patients (TYPE 2) and controls (CON) ( n = 6 for both). During the clamp arterio-venous glucose extraction was higher in CON versus TYPE 2 in the arm (6.9 ± 1.0 versus 4.7 ± 0.8%; mean ± s.e.m. ; P = 0.029), but not in the leg (4.2 ± 0.8 versus 3.1 ± 0.6%). Blood flow was not different between CON and TYPE 2 but was higher ( P < 0.05) in arm versus leg (CON: 74 ± 8 versus 56 ± 5; TYPE 2: 87 ± 9 versus 43 ± 6 ml min⁻¹ kg⁻¹ muscle, respectively). At basal, CON had 84% higher arm GC ( P = 0.012) and 87% higher leg GC ( P = 0.016) compared with TYPE 2. During clamp, the difference between CON and TYPE 2 in arm GC was diminished to 54% but maintained at 80% in the leg. In conclusion, this study shows that glucose clearance is higher in arm than leg muscles, regardless of insulin resistance, which may indicate better preserved insulin sensitivity in arm than leg muscle in type 2 diabetes.     

Neurovascular responses to mental stress

The effects of mental stress (MS) on muscle sympathetic nerve activity (MSNA) and limb blood flows have been studied independently in the arm and leg, but they have not been studied collectively. Furthermore, the cardiovascular implications of postmental stress responses have not been thoroughly addressed. The purpose of the current investigation was to comprehensively examine concurrent neural and vascular responses during and after mental stress in both limbs. In Study 1, MSNA, blood flow (plethysmography), mean arterial pressure (MAP) and heart rate (HR) were measured in both the arm and leg in 12 healthy subjects during and after MS (5 min of mental arithmetic). MS significantly increased MAP (Δ15 ± 3 mmHg; P < 0.01) and HR (Δ19 ± 3 beats min⁻¹; P < 0.01), but did not change MSNA in the arm (14 ± 3 to 16 ± 3 bursts min⁻¹; n = 6) or leg (14 ± 2 to 15 ± 2 bursts min⁻¹; n = 8). MS decreased forearm vascular resistance (FVR) by −27 ± 7% ( P < 0.01; n = 8), while calf vascular resistance (CVR) did not change (−6 ± 5%; n = 11). FVR returned to baseline during recovery, whereas MSNA significantly increased in the arm (21 ± 3 bursts min⁻¹; P < 0.01) and leg (19 ± 3 bursts min⁻¹; P < 0.03). In Study 2, forearm and calf blood flows were measured in an additional 10 subjects using Doppler ultrasound. MS decreased FVR (−27 ± 10%; P < 0.02), but did not change CVR (5 ± 14%) as in Study 1. These findings demonstrate differential vascular control of the arm and leg during MS that is not associated with muscle sympathetic outflow. Additionally, the robust increase in MSNA during recovery may have acute and chronic cardiovascular implications.     

Acute dopamine/noradrenaline reuptake inhibition enhances human exercise performance in warm, but not temperate conditions

Nine healthy endurance-trained males were recruited to examine the effect of a dual dopamine/noradrenaline reuptake inhibitor on performance, thermoregulation and the hormonal responses to exercise. Subjects performed four trials, ingesting either a placebo (pla) or 2 × 300 mg bupropion (bup), prior to exercise in temperate (18°C) or warm (30°C) conditions. Trials consisted of 60 min cycle exercise at 55% W _max immediately followed by a time trial (TT). TT performance in the heat was significantly improved by bupropion (pla: 39.8 ± 3.9 min, bup: 36.4 ± 5.7 min; P = 0.046), but no difference between treatments was apparent in temperate conditions (pla: 30.6 ± 2.2 min, bup: 30.6 ± 1.9 min; P = 0.954). While TT power output was consistently lower in the heat when compared to temperate conditions, this decrement was attenuated by bupropion. At the end of the TT in the heat, both core temperature (pla 39.7 ± 0.3°C, bup 40.0 ± 0.3°C; P = 0.017) and HR (pla 178 ± 7 beats min⁻¹, bup 183 ± 12 beats min⁻¹; P = 0.039), were higher in the bupropion trial than in the placebo. Circulating pituitary and adrenal hormone concentrations increased throughout exercise in all trials. Circulating serum prolactin was elevated above temperate levels during exercise in a warm environment ( P < 0.001). These data indicate that performance in warm conditions is enhanced by acute administration of a dual dopamine/noradrenaline reuptake inhibitor. No such effect was apparent under temperate conditions. It appears that bupropion enabled subjects to maintain a greater TT power output in the heat with the same perception of effort and thermal stress reported during the placebo trial, despite the attainment of a higher core temperature.     

Exercise Increases Ca2+–Calmodulin-Dependent Protein Kinase II Activity in Human Skeletal Muscle

There is evidence in rodents that Ca²⁺-calmodulin-dependent protein kinase II (CaMKII) activity is higher in contracting skeletal muscle, and this kinase may regulate skeletal muscle function and metabolism during exercise. To investigate the effect of exercise on CaMKII in human skeletal muscle, healthy men (   n = 8  ) performed cycle ergometer exercise for 40 min at 76 ± 1 % peak pulmonary O₂ uptake (_O2peak), with skeletal muscle samples taken at rest and after 5 and 40 min of exercise. CaMKII expression and activities were examined by immunoblotting and in vitro kinase assays, respectively. There were no differences in maximal (+ Ca²⁺, CaM) CaMKII activity during exercise compared with rest. Autonomous (- Ca²⁺, CaM) CaMKII activity was 9 ± 1 % of maximal at rest, remained unchanged at 5 min, and increased to 17 ± 1 % (   P < 0.01  ) at 40 min. CaMKII autophosphorylation at Thr²⁸⁷ was 50-70 % higher during exercise, with no differences in CaMKII expression. The effect of maximal aerobic exercise on CaMKII was also examined (   n = 9  ), with 0.7- to 1.5-fold increases in autonomous CaMKII activity, but no change in maximal CaMKII activity. CaMKIV was not detected in human skeletal muscle. In summary, exercise increases the activity of CaMKII in skeletal muscle, suggesting that it may have a role in regulating skeletal muscle function and metabolism during exercise in humans.     

The contribution of intrapulmonary shunts to the alveolar-to-arterial oxygen difference during exercise is very small

Exercise is well known to cause arterial     to fall and the alveolar–arterial     difference (Aa     ) to increase. Until recently, the physiological basis for this was considered to be mostly ventilation/perfusion     /     inequality and alveolar–capillary diffusion limitation. Recently, arterio-venous shunting through dilated pulmonary blood vessels has been proposed to explain a significant part of the Aa     during exercise. To test this hypothesis we determined venous admixture during 5 min of near-maximal, constant-load, exercise in hypoxia (in inspired O₂ fraction,     , 0.13), normoxia (     , 0.21) and hyperoxia (     , 1.0) undertaken in balanced order on the same day in seven fit cyclists (     , 61.3 ± 2.4 ml kg⁻¹ min⁻¹; mean ± s.e.m. ). Venous admixture reflects three causes of hypoxaemia combined: true shunt, diffusion limitation and     /     inequality. In hypoxia, venous admixture was 22.8 ± 2.5% of the cardiac output; in normoxia it was 3.5 ± 0.5%; in hyperoxia it was 0.5 ± 0.2%. Since only true shunt accounts for venous admixture while breathing 100% O₂, the present study suggests that shunt accounts for only a very small portion of the observed venous admixture, Aa     and hypoxaemia during heavy exercise.     

Attenuated vascular responsiveness to noradrenaline release during dynamic exercise in dogs

During dynamic exercise, there is reduced responsiveness to α₁- and α₂-adrenergic receptor agonists in skeletal muscle vasculature. However, it is desirable to examine the sympathetic responsiveness to endogenous release of neurotransmitter, since exogenous sympathomimetic agents are dependent upon their ability to reach the abluminal receptor. Therefore, to further our understanding of sympathetic control of vasomotor tone during exercise, we employed a technique that would elicit the release of endogenous noradrenaline (norepinephrine) during dynamic exercise. Mongrel dogs ( n = 8, 19-24 kg) were instrumented chronically with transit time ultrasound flow probes on both external iliac arteries. A catheter was placed in a side branch of the femoral artery for intra-arterial administration of tyramine, an agent which displaces noradrenaline from the nerve terminal. Doses of 0.5, 1.0 and 3.0 μg ml⁻¹ min⁻¹ of iliac blood flow were infused for 1 min at rest and during graded intensities of exercise. Dose-related decreases in iliac vascular conductance were achieved with these concentrations of tyramine. The reductions in iliac vascular conductance (means ± s.e.m .) were 45 ± 6 %, 30 ± 4 %, 26 ± 3 % and 17 ± 2 %, for the 1.0 μg ml⁻¹ min⁻¹ dose at rest, 3.0 miles h⁻¹, 6.0 miles h⁻¹ and 6.0 miles h⁻¹, 10 % gradient, respectively. At all doses, the magnitude of vasoconstriction caused by administration of tyramine was inversely related to workload. We conclude that there is a reduced vascular responsiveness to sympathoactivation in dynamically exercising skeletal muscle.     

Fuel selection in Wistar rats exposed to cold: shivering thermogenesis diverts fatty acids from re-esterification to oxidation

This study characterizes the effects of shivering thermogenesis on metabolic fuel selection in Wistar rats. Because lipids account for most of the heat produced, we have investigated: (1) whether the rate of appearance of non-esterified fatty acids ( R _a NEFAs) is stimulated by shivering, (2) whether mono-unsaturated (oleate) and saturated fatty acids (palmitate) are affected similarly, and (3) whether the partitioning between fatty acid oxidation and re-esterification is altered by cold exposure. Fuel oxidation was measured by indirect calorimetry and fatty acid mobilization by continuous infusion of 9,10-[³H]oleate and 1-[¹⁴C]palmitate. During steady-state cold exposure, results show that total heat production is unequally shared by the oxidation of lipids (52% of metabolic rate), carbohydrates (35%) and proteins (13%), and that the same fuel selection pattern is observed at all shivering intensities. All previous research shows that mammals stimulate R _a NEFA to support exercise or shivering. In contrast, results reveal that the R _a NEFA of the rat remains constant during cold exposure (∼55 μmol kg⁻¹ min⁻¹). No preferential use of mono-unsaturated over saturated fatty acids could be demonstrated. The rat decreases its rate of fatty acid re-esterification from 48.4 ± 6.4 to 19.6 ± 6.3 μmol kg⁻¹ min⁻¹ to provide energy to shivering muscles. This study is the first to show that mammals do not only increase fatty acid availability for oxidation by stimulating R _a NEFA. Reallocation of fatty acids from re-esterification to oxidation is a novel, alternative strategy used by the rat to support shivering.     

Limb neurovascular control during altered otolithic input in humans

Head-down rotation (HDR), which activates the vestibulosympathetic reflex, increases leg muscle sympathetic nerve activity (MSNA) and produces calf vasoconstriction with no change in either cardiac output or arterial blood pressure. Based on animal studies, it was hypothesized that differential control of arm and leg MSNA explains why HDR does not alter arterial blood pressure. Fifteen healthy subjects were studied. Heart rate, arterial blood pressure, forearm and calf blood flow, and leg MSNA responses were measured during HDR in these subjects. Simultaneous recordings of arm and leg MSNA were obtained from five of the subjects. Forearm and calf blood flow, vascular conductances, and vascular resistances were similar before HDR, as were arm and leg MSNA. HDR elicited similar significant increases in leg (Δ6 ± 1 bursts min⁻¹; 59 ± 16 % from baseline) and arm MSNA (Δ5 ± 1 bursts min⁻¹; 80 ± 28 % from baseline). HDR significantly decreased calf (−19 ± 2 %) and forearm vascular conductance (−12 ± 2 %) and significantly increased calf (25 ± 4 %) and forearm vascular resistance (15 ± 2 %), with ∼60 % greater vasoconstriction in the calf than in the forearm. Arterial blood pressure and heart rate were not altered by HDR. These results indicate that there is no differential control of MSNA in the arm and leg during altered feedback from the otolith organs in humans, but that greater vasoconstriction occurs in the calf than in the forearm. These findings indicate that vasodilatation occurs in other vascular bed(s) to account for the lack of increase in arterial blood pressure during HDR.     

Differential effect of angiotensin II on blood circulation in the renal medulla and cortex of anaesthetised rats

The renal medulla is sensitive to hypoxia, and a depression of medullary circulation, e.g. in response to angiotensin II (Ang II), could endanger the function of this zone. Earlier data on Ang II effects on medullary vasculature were contradictory. The effects of Ang II on total renal blood flow (RBF), and cortical and medullary blood flow (CBF and MBF: by laser-Doppler flux) were studied in anaesthetised rats. Ang II infusion (30 ng kg⁻¹ min⁻¹ i.v. ) decreased RBF 27 ± 2 % (mean ± s.e.m. ), whereas MBF increased 12 ± 2 % (both P < 0.001). Non-selective blockade of Ang II receptors with saralasin (3 μg kg⁻¹ min⁻¹ i.v. ) increased RBF 12 ± 2 % and decreased MBF 8 ± 2 % ( P < 0.001). Blockade of AT₁ receptors with losartan (10 mg kg⁻¹) increased CBF 10 ± 2 % ( P < 0.002) and did not change MBF. Losartan given during Ang II infusion significantly increased RBF (53 ± 7 %) and decreased MBF (27 ± 7 %). Blockade of AT₂ receptors with PD 123319 (50 μg kg⁻¹ min⁻¹ i.v. ) did not change CBF or MBF. Intramedullary infusion of PD 123319 (10 μg min⁻¹) superimposed on intravenous Ang II infusion did not change RBF, but slightly decreased MBF (4 ± 2 %, P < 0.05). We conclude that in anaesthetised surgically prepared rats, exogenous or endogenous Ang II may not depress medullary circulation. In contrast to the usual vasoconstriction in the cortex, vasodilatation was observed, possibly related to secondary activation of vasodilator paracrine agents rather than to a direct action via AT₂ receptors.     

Prediction of peak oxygen uptake from sub-maximal ratings of perceived exertion elicited during a graded exercise test in obese women

The purpose was to assess the validity of predicting peak oxygen uptake     from Ratings of Perceived Exertion (RPE)≤15, during a graded exercise test (GXT), in obese women. Forty-three obese women performed GXT to volitional exhaustion. During GXT, oxygen uptake     and RPE were measured. Individual linear regressions between     and RPE≤15 were extrapolated to RPE 20 in order to predict     . Actual and predicted     were not significantly different (13.9±3.0 vs 14.2±3.3 ml kg⁻¹ min⁻¹, respectively; p =.26). The Pearson product moment correlation between actual and predicted     was high ( r =0.82). The 95% limits of agreement analysis on these values (bias±1.96SD) was −0.3±3.7 ml kg⁻¹ min⁻¹. Results suggested that RPE≤15 elicited during a sub-maximal GXT provides accurate     prediction. Therefore, it is not necessary to perform GXT to voluntary exhaustion to determine     in obese women.     

Cerebral ammonia uptake and accumulation during prolonged exercise in humans

We evaluated whether peripheral ammonia production during prolonged exercise enhances the uptake and subsequent accumulation of ammonia within the brain. Two studies determined the cerebral uptake of ammonia (arterial and jugular venous blood sampling combined with Kety–Schmidt-determined cerebral blood flow; n = 5) and the ammonia concentration in the cerebrospinal fluid (CSF; n = 8) at rest and immediately following prolonged exercise either with or without glucose supplementation. There was a net balance of ammonia across the brain at rest and at 30 min of exercise, whereas 3 h of exercise elicited an uptake of 3.7 ± 1.3 μmol min⁻¹ (mean ± s.e.m. ) in the placebo trial and 2.5 ± 1.0 μmol min⁻¹ in the glucose trial ( P < 0.05 compared to rest, not different across trials). At rest, CSF ammonia was below the detection limit of 2 μ m in all subjects, but it increased to 5.3 ± 1.1 μ m following exercise with glucose, and further to 16.1 ± 3.3 μ m after the placebo trial ( P < 0.05). Correlations were established between both the cerebral uptake  ( r ²= 0.87; P < 0.05)  and the CSF concentration  ( r ²= 0.72; P < 0.05)  and the arterial ammonia level and, in addition, a weaker correlation  ( r ²= 0.37; P < 0.05)  was established between perceived exertion and CSF ammonia at the end of exercise. The results let us suggest that during prolonged exercise the cerebral uptake and accumulation of ammonia may provoke fatigue, e.g. by affecting neurotransmitter metabolism.     

No effect of growth hormone administration on substrate oxidation during exercise in young, lean men

The purpose of this study was to examine the effects of increased fat availability induced by growth hormone (GH) administration on the oxidative metabolism during exercise. Seven well-trained males (age 25 ± 2 years (mean ± s.e.m. ); peak oxygen consumption     : 62 ± 1 ml min⁻¹ kg⁻¹ (completed four randomised trials: 120 min bicycling at 55%     4 h after receiving either 7.5 IU (2.5 mg) GH or placebo (Plc), and during rest after receiving either GH or Plc. In all studies a standardized meal was given 2 h after GH or Plc injection. GH administration resulted in an ∼60-fold increase in serum GH concentration at rest ( P < 0.0001) and during exercise ( P < 0.0001). The increase in serum GH was followed by an increase in circulating glycerol at rest (8%, P < 0.0001). When combined with exercise the increase in plasma glycerol was more pronounced (GH: 716% of baseline versus Plc: 328%, P < 0.0001). However, this increase in fat mobilization did not increase fat oxidation during exercise (indirect calorimetry). In conclusion, GH administration combined with aerobic exercise increased lipolytic parameters substantially more than exercise alone, but did not further augment whole body fat oxidation.