This study examines the precise time course that brown adipose tissue (BAT) takes to adopt the characteristics of white adipose tissue in postnatal lambs. Perirenal adipose tissue was sampled from ewe-reared lambs within 1 h of birth and at 1, 2, 4, 7, 14, 21 and 30 days of age and analysed for the amount of mRNA for uncoupling protein (UCP), the amount and activity of UCP, and protein, mitochondrial protein and lipid content. This was combined with measurements of colonic temperature and jugular venous plasma concentrations of thyroid hormones and insulin-like growth factor-1 (IGF-1). Over the first 4-7 days of age, large quantities of UCP mRNA were associated with a peak in plasma triiodothyronine concentration at 2 days of age followed by a maximal amount and activity of UCP at 4 days and a basal colonic temperature of 39·3°C. Between 7 and 30 days there was a large increase in lipid deposition as the amount and activity of UCP and the amount of UCP mRNA declined to basal values and colonic temperature was maintained at 40°C. A significant positive relationship between perirenal adipose tissue lipid content and plasma IGF-1 concentration was observed throughout the study period. It is concluded that ovine adipose tissue maturation occurs in two distinct phases over the first month of life. The precise time scale of this process could be regulated in part by the lamb's body temperature which determines whether adipose tissue is required for heat production (i.e. BAT) or as an endogenous energy source (i.e. white adipose tissue).

We examined the effect of caffeine co-ingested with either carbohydrate or fat on metabolism and performance in eight endurance-trained subjects who performed a random order of four experimental trials consisting of 120 min of steady-state ergometer cycling at 70 % of maximal O2 uptake (SS) followed by a time trial in which subjects completed a set amount of work (7 kJ kg-1) as quickly as possible. One hour before SS subjects ingested either 2.6 g kg-1 carbohydrate (CHO); 2.6 g kg-1 CHO + 6 mg kg-1 caffeine (CHO + CAF); 1.2 g kg-1 fat with 2000 U I.V. heparin (FAT); or 1.2 g kg-1 fat with 2000 U I.V. heparin + 6 mg kg-1 caffeine (FAT + CAF). The rate of carbohydrate oxidation was higher (µmol kg-1 min-1: CHO, 243 ± 39 and CHO + CAF, 239 ± 30 vs. FAT, 196 ± 48 and FAT + CAF, 191 ± 55; P < 0.05, values are means ± S.D.) and the rate of fat oxidation lower (µmol kg-1 min-1: CHO, 19 ± 8 and CHO + CAF, 22 ± 7 vs. FAT, 35 ± 19 and FAT + CAF, 37 ± 17; P < 0.05) with carbohydrate than fat ingestion. Yet despite lower carbohydrate use with fat feeding, the time taken to complete the time trial was less after carbohydrate than after fat ingestion (min: CHO, 30.37 ± 7.42 and CHO + CAF, 29.12 ± 5.62 vs. FAT, 33.02 ± 8.50 and FAT + CAF, 32.78 ± 7.70; P < 0.05). We conclude that (1) caffeine co-ingested with either carbohydrate or fat meals has no additive effect on substrate utilization or exercise performance and (2) carbohydrate ingestion before exercise improves subsequent time trial performance compared with fat ingestion. Experimental Physiology (2001) 86.1, 137-144.

We studied the development of nutritional iron deficiency 0, 10, 20, 30 and 40 days after the intake of a semisynthetic diet lacking iron (diet 0) and the possible interactions with calcium, phosphorus and magnesium in both control rats and rats after 40 days of iron deficiency. During this period, iron deficiency was found to produce stress in the rats, as evidenced by high levels of cortisol in the serum. High levels of parathyroid hormone (PTH) were also found. There was a considerable increase in the absorption of calcium, phosphorus and magnesium, but the phosphorus and magnesium balance decreased and that of calcium remained practically unchanged, although there was an increase in calcium urinary elimination. Despite the noticeable degree of bone demineralization, which was evident in the femur, serum levels of calcium, phosphorus and magnesium remained constant. The present study shows that severe nutritional ferropenic anaemia provokes significant alterations in the metabolism of calcium, phosphorus and magnesium. We conclude that these alterations should be taken into account in the treatment of this pathology, given its prevalence and the fact that it may exacerbate other pathologies, particularly those related to the metabolism of calcium and phosphorus.

Isometric exercise training has been shown to reduce resting blood pressure, but the effect that this might have on orthostatic tolerance is poorly understood. Changes in orthostatic tolerance may also be dependent on whether the upper or lower limbs of the body are trained using isometric exercise. Twenty-seven subjects were allocated to either a training or control group. A training group first undertook 5 weeks of isometric exercise training of the legs, and after an 8 week intervening period, a second training group containing six subjects from the initial training group, undertook 5 weeks of isometric arm-training. The control group were asked to continue their normal daily activities throughout the 18 weeks of the study. In all subjects orthostatic tolerance, assessed using lower body negative pressure (LBNP), and resting blood pressure were measured before and after each of the 5 week training or control periods. Estimated lean leg volume was determined before and after leg-training. During all LBNP tests, heart rate and blood pressure were recorded each minute, and the time taken to reach the highest heart rate was derived (time to peak HR). Resting systolic blood pressure (mean ± S.D.), when measured during the last week of training, was significantly reduced after both leg (−10 ± 8.7 mmHg) and arm (−12.4 ± 9.3 mmHg; P<0.05) isometric exercise training, compared to controls. This reduction disappeared when blood pressure was measured immediately before the LBNP tests, which followed training. Orthostatic tolerance only increased after leg-training (20.8 ± 16.4 LTI; P<0.05) and was accompanied by an increased time to peak HR (119.8 ± 106.3 beats min−1; P<0.05) in this group. Blood pressure responses to LBNP did not change after arm-training, leg-training or in controls (P>0.05). There was a small but significant increase in estimated lean leg volume after leg-training (0.1 ± 0.1 l; P<0.05). These results suggest that lower resting blood pressure is probably not responsible for the increased orthostatic tolerance after isometric exercise training of the legs. Rather, it is possible that the training altered some other aspect of cardiovascular control during orthostatic stress that was apparent in the changes in heart rate. Legtraining was accompanied by increases in estimated lean leg volume. The effects of isometric training on orthostatic tolerance appear to be specific to limbs that are directly involved in LBNP testing.

Dependent upon the relative speed of pulmonary oxygen consumption (V˙O2) and blood flow (Q˙) kinetics, the exercise off-transient may represent a condition of sub- or supra-optimal perfusion. To date, there are no direct measurements of the dynamics of the V˙O2/Q˙ relationship within the muscle at the onset of the work/recovery transition. To address this issue, microvascular PO2 (PO2,m) dynamics were studied in the spinotrapezius muscles of 11 female Sprague-Dawley rats (weight ~220 g) during and following electrical stimulation (1 Hz) to assess the adequacy of Q˙ relative to V˙O2 post exercise. The exercise blood flow response (radioactive microspheres: muscle Q˙ increased ~240 %), and post-exercise arterial blood pH (7.40 ± 0.02) and blood lactate (1.3 ± 0.4 mM l-1) values were consistent with moderate-intensity exercise. Recovery PO2,m (i.e. off-transient) rose progressively until baseline values were achieved (Δend-recovery exercise PO2,m, 14.0 ± 1.9 Torr) and at no time fell below exercising PO2,m. The off-transient PO2,m was well fitted by a dual exponential model with both fast (τ = 25.4 ± 5.1 s) and slow (τ = 71.2 ± 34.2 s) components. Furthermore, there was a pronounced delay (54.9 ± 10.7 s) before the onset of the slow component. These data, obtained at the muscle microvascular level, support the notion that muscle V˙O2 falls with faster kinetics than muscle Q˙ during the off-transient, such that PO2,m increases systematically, though biphasically, during recovery. Experimental Physiology (2001) 86.3, 349-356.

During acclimatization to the hypoxia of altitude, the cerebral circulation is exposed to arterial hypoxia and hypocapnia, two stimuli with opposing influences on cerebral blood flow (CBF). In order to understand the resultant changes in CBF, this study examined the responses of CBF during a period of constant mild hypoxia both with and without concomitant regulation of arterial PCO2. Nine subjects were each exposed to two protocols in a purpose-built chamber: (1) 48 h of isocapnic hypoxia (Protocol I), where end-tidal PO2 (PET,O2) was held at 60 Torr and end-tidal PCO2 (PET,CO2) at the subject's resting value prior to experimentation; and (2) 48 h of poikilocapnic hypoxia (Protocol P), where PET,O2 was held at 60 Torr and PET,CO2 was uncontrolled. Transcranial Doppler ultrasound was used to assess CBF. At 24 h intervals during and after the hypoxic exposure CBF was measured and the sensitivity of CBF to acute variations in PO2 and PCO2 was determined. During Protocol P, PET,CO2 decreased by 13 % (P < 0.001) and CBF decreased by 6 % (P < 0.05), whereas during Protocol I, PET,CO2 and CBF remained unchanged. The sensitivity of CBF to acute variations in PO2 and PCO2 increased by 103 % (P < 0.001) and 28 % (P < 0.01), respectively, over the 48 h period of hypoxia. These changes did not differ between protocols. In conclusion, CBF decreases during mild poikilocapnic hypoxia, indicating that there is a predominant effect on CBF of the associated arterial hypocapnia. This fall occurs despite increases in the sensitivity of CBF to acute variations in PO2/PCO2 arising directly from the hypoxic exposure. Experimental Physiology (2002) 87.5, 633-642.

Phloridzin-insensitive D-glucose uptake into enterocytes isolated sequentially from along the crypt-villus axis showed the majority of transport activity to reside in cells from the upper third of the villus. In contrast, total postnuclear glucose transporter 2 (GLUT2) protein content of the cells was high even close to the crypt and was almost constant for the upper 80 % of the villi. A 4 h lumenal perfusion in vivo with 100 mM D-glucose prior to harvesting the enterocytes produced a 2- to 3-fold increase in phloridzin-insensitive D-glucose uptake which extended down 70 % of the villus. Vascular infusion in vivo with either 800 pM gastric inhibitory polypeptide (GIP) or glucagon-like peptide-2 (GLP-2) prior to harvesting enterocytes produced the same response as lumenal glucose, while glucagon like peptide-1 (GLP-1) had no effect. Inclusion of 30 µM brefeldin A (BFA), an inhibitor of protein trafficking, in the lumenal perfusate produced a small, but not significant, increase in the control uptake profile along the villus in isolated enterocytes. However, BFA significantly reduced the upregulation induced by lumenal glucose and vascular GIP and blocked the stimulation produced by vascular GLP-2. Biotinylation of surface proteins and isolation with protein A indicated that there was no change in the membrane abundance of GLUT2 after GLP-2 treatment. These results are discussed in relation to the role of gastrointestinal peptide hormones in controlling intestinal hexose transport and the possibility of protein trafficking being involved in mediating the upregulation of GLUT2 activity in the enterocyte basolateral membrane.

Effects of brief postganglionic vagal nerve stimulation on the activation sequence of the rabbit sinoatrial (SA) node were investigated. Activation sequences in a small area (7 mm × 7 mm) on the epicardial surface were measured in a beat-to-beat manner using an extracellular potential mapping system composed of 64 modified bipolar electrodes with high-gain and low-frequency band-pass filtering. The leading pacemaker site was recognised clearly from both the activation sequence and the characteristic morphology of the potentials. Vagal stimulation resulted in a short-lasting initial slowing of spontaneous rate followed by a long-lasting secondary slowing; a brief period of relative or absolute acceleration was interposed between the two slowing phases. During these changes of spontaneous rate, the leading pacemaker site shifted in a complex beat-to-beat manner by 1-6 mm alongside the crista terminalis in the superior or inferior direction. For the first spontaneous excitation following stimulation, the greater the slowing, the larger the distance of the pacemaker shift. There was no such linear relationship between the extent of slowing and the distance of pacemaker shift for the subsequent beats. These changes in the leading pacemaker site in response to vagal stimulation may be the result of the functional and morphological heterogeneity of the mammalian SA node in terms of innervation, receptor distribution and ion channel densities. Experimental Physiology (2001) 86.2, 177-184.

Vagal cardioinhibition is exerted through a reduction not only in the heart rate but also in the rate of propagation of the cardiac action potential and in myocardial contractility. In several species, such effects can be produced independently by selective activation of ganglia in identified 'fat pads'. In this study we investigate differential control of heart rate and atrioventricular conduction by two ganglionic clusters in the rat, a species increasingly important in studies of cardiovascular control. Epicardial sites producing low-threshold changes in P-P and P-R interval of the ECG in an arterially perfused preparation were explored with concentric bipolar stimulating electrodes. Stimulation sites centred on two principal ganglia, the sinoatrial (SA) ganglion at the junction of the right superior vena cava and right atrium, and the atrioventricular (AV) ganglion at the junction of the inferior pulmonary veins and left atrium. Stimulation of the SA ganglion decreased heart rate in all preparations, with little or no effect on AV conduction in one-third. Stimulation of the AV ganglion consistently slowed conduction without eliciting a comparable bradycardia. Responses survived blockade of ganglionic transmission by trimetaphan, with an enhanced chronotropic selectivity to SA ganglion stimulation, suggesting that co-excitation of preganglionic elements en passant may have contributed to the earlier mixed responses. Effective stimulation sites were precisely circumscribed and corresponded to principal ganglionic clusters confirmed histologically. We conclude that cardiac vagal ganglia in the rat show a topographical functional organisation and are amenable to investigation using the arterially perfused preparation. Experimental Physiology (2003) 88.3, 315-327.

Within the last decade huge advances have been made in the understanding of the interactions between the central nervous system (CNS) and the immune system. Foremost amongst these is the realization that cytokines, classically regarded as mediators and co-ordinators of the inflammatory and immune responses, can exert a number of neuromodulatory effects within the CNS under both physiological and pathological conditions (for recent reviews see Rothwell & Hopkins, 1995; Rothwell et al. 1997; Rothwell, 1999). Consistent with this, it has been shown that many cytokines and their receptors are present in the brain (Hopkins & Rothwell, 1995). Much attention has focused on the pro-inflammatory cytokine interleukin-1 (IL-1) especially the [beta] variant. IL-1[beta] has been shown to be produced in the CNS in response to a number of stimuli including peripheral administration of lipopolysaccharide (LPS); traumatic brain injury; acute stress; anorexia and [beta]-adrenoceptor agonist administration (e.g. Maruta et al. 1997). IL-1 receptors have also been shown to be present in many brain regions, with high levels in the hippocampus and hypothalamus (Ban et al. 1991). Expression of IL-1 receptors has also been shown to be upregulated in response to insult, e.g. kainic acid administration (Nishiyori et al. 1997) and expression is higher in aged animals (Murray & Lynch, 1998). However this review will concentrate on the effects of IL-1[beta] on hippocampal synaptic transmission and long-term potentiation (LTP), a process long thought to be an important underlying mechanism of learning and memory formation (for review see Bliss & Collingridge, 1993).

Blast injuries represent a problem for civilian and military populations. Primary thoracic blast injury causes a triad of bradycardia, hypotension and apnoea. The objective of this study was to investigate the reflex nature of this response and its modulation by vagotomy or administration of atropine. The study was conducted on terminally anaesthetised (alphadolone/alphaxalone, 18-24 mg kg h-1, I.V.) male Wistar rats randomly allocated to the groups indicated below. Blast injuries were produced with compressed air while sham blast involved the sound of a blast only. Primary blast injury to the thorax resulted in a bradycardia (measured as an increase in the interval between beats, or heart period (HP) to 489 ± 37 ms from 133 ± 3 ms with a latency of onset of 4.3 ± 0.3 s, mean ± S.E.M.), hypotension (fall in mean arterial blood pressure (MBP) from 128.1 ± 3.7 mmHg to 34.8 ± 4.1 mmHg, latency of onset 2.0 ± 0.1 s) and apnoea lasting 28.3 ± 2.3 s. Sham blast had no effect. The bradycardia and apnoea following thoracic blast were abolished by cervical vagotomy while the hypotension was attenuated. Atropine (0.3 mg kg-1, I.V.) caused a significant reduction in the bradycardia (HP increasing from 124 ± 3 ms to 142 ± 4 ms) but did not modulate either the hypotension or apnoea. It is concluded that a reflex involving the vagus nerve mediates the bradycardia, apnoea and a component of the hypotension associated with thoracic blast. The pattern of this response is similar to effects that follow stimulation of the pulmonary afferent C-fibres. Experimental Physiology (2001) 86.3, 357-364.

The hypotensive and vasorelaxing peptides adrenomedullin (AM) and its gene-related peptide, proadrenomedullin N-terminal 20 peptide (PAMP), were found to be distributed on the surface of the colonic mucosa. AM and PAMP showed dose-dependent antimicrobial activity against E. coli. The results suggest that the novel vasoactive peptides AM and PAMP play an important role in mucosal defence. Experimental Physiology (2001) 86.5, 543-545.

Cardiac hypertrophy is a general term signifying an increase in cardiac mass in response to applied stress. In mild, early hypertrophy, cardiac myocyte contractile performance may be normal or enhanced, whereas in severe hypertrophy associated with cardiac failure, myocyte contraction is reduced in amplitude and increased in duration. In contrast to the varied contractile response, the duration of electrical excitation shows similar changes in both mild and severe hypertrophy. Action potential duration in mid-myocardial and sub-epicardial layers is increased, which is associated with ventricular arrhythmias (in a similar manner to the long QT syndromes from other causes), based on afterdepolarizations and enhanced automaticity. Single-cell studies following exercise training in animal models show that exercise-induced cardiac hypertrophy displays features similar to mild, compensated hypertrophy from other causes. Developed shortening of unloaded single cells is increased or unchanged, and developed force in single myocytes is enhanced. Action potential duration is increased, apart from in the sub-endocardial layer. As with mild hypertrophy from other causes, this will be pro-arrhythmic because of altered dispersion of repolarization and enhanced automaticity. Major abnormalities of the ECG in man include frequent and complex ventricular ectopy, ST segment changes and prolongation of repolarization. In this review a case is presented for regarding exercise-induced cardiac hypertrophy as being no different from mild cardiac hypertrophy resulting from other, pathological causes. The cellular electrophysiological changes are sufficient to account for many of the abnormalities of the ECG, including high-grade ventricular ectopy. Sudden death in trained athletes who have no evidence of specific heart disease may be a direct consequence of cardiac hypertrophy and altered repolarization. Experimental Physiology (2003) 88.5, 639-644.

To determine to what extent exposure to high ambient temperature and feeding level affect tissue energy metabolism in piglets, regional blood flow and oxidative capacity of tissues were evaluated in sixteen 21.8 ± 2.8 kg pigs. At 5 weeks of age, littermates were divided into three groups and acclimated to the treatment for 25 days. One group was reared at 33°C and fed ad libitum (33AL, n = 6) while the other two groups were maintained at 23°C and either pair-fed on the basis of the food consumption of their 33AL littermates (23PF, n = 5), or fed ad libitum (23AL, n = 5). Regional blood flow was determined in conscious pigs by injection of coloured microspheres, which were recovered in different tissues after slaughter. Activities of cytochrome oxidase and cytochrome aa3 content were measured in tissue homogenates of heart, longissimus dorsi and rhomboideus muscles, liver and small intestine. There was decreased blood flow to internal adipose tissue (42 %) and increased blood flow to peripheral tissues (skin, 44 %) and tissues implicated in respiratory evaporative heat loss (diaphragm, 45 %, lungs, 59 %) at 33°C compared to 23°C, which can be viewed as an effective mechanism for increasing heat loss at high temperature. In addition, the concomitant decrease in blood flow (49 %) and slight reduction of oxidative capacities in both muscles at 33°C might contribute to the reduction in thermogenesis, but these effects were also observed when the feeding level was reduced at thermal neutrality (23PF group). In the viscera (intestine, liver), blood flow was decreased in the two groups on a restricted food intake (about 50 % of 23AL), independently of environmental temperature. The results suggest that most of the mechanisms associated with the reduction in energy expenditure during warm acclimation are related to the adaptive reduction in food intake. Experimental Physiology (2001) 86.1, 83-91.

Cross-sectional studies have compared the oxygen uptake (VO2 ) kinetics during the on-transient of moderate intensity exercise in older and younger adults. The slower values in the older adults may have been due to an age-related reduction in the capacity for O2 transport or alternatively a reduced intramuscular oxidative capacity. We studied: (1) the effects of ageing on VO2 kinetics in older adults on two occasions 9 years apart, and (2) the effect of hyperoxia on VO2 kinetics at the second test time. After a 9 year period, follow-up testing was undertaken on seven older adults (78 ± 5 years, mean ± S.D.). They each performed six repeats of 6 min bouts of constant-load cycle exercise from loadless cycling to 80 % of their ventilatory threshold. They breathed one of two gas mixtures (euoxia: inspired O2 fraction, FI,O2, 0á21; hyperoxia: FI,O2, 0á70) on different trials determined on a random basis. Breath-by-breath VO2 data were time aligned and ensemble averaged. VO2 kinetics, modelled with a single exponential from phase 2 onset (+20 s) to steady state and described by the exponential time constant ([tau]) were compared with data collected from the same adults 9 years earlier. One-way repeated measures analysis of variance revealed that [tau] was slowed significantly with age (from 30 ± 8 to 46 ± 10 s), but was unaffected by hyperoxia (43 ± 15 s). We concluded that: (1) in older adults studied longitudinally over a 9 year period, the on-transient VO2 kinetics are slowed, in agreement with, but to a greater extent, than from cross-sectional data; and (2) the phase 2 time constant ([tau]) for these older adults was not accelerated by hyperoxic breathing. Thus the expected hyperoxia-induced increase in the capacity for O2 transport was not associated with faster on-transient VO2 kinetics suggesting either that O2 transport may not limit VO2 kinetics during the 8th decade, or that O2 transport was not improved with hyperoxia.

For moderate work rates (i.e. below the lactate threshold, [theta]L), oxygen uptake ([Vdot]O2) approaches the steady state mono-exponentially. At higher work rates, the [Vdot]O2 kinetics are more complex, reflecting the delayed superimposition of an additional, slow component. The mechanisms of this ‘slow’ component are poorly understood. It has been demonstrated, however, that while a prior bout of supra-[theta]L cycling (with a 6 min recovery) does not significantly affect the [Vdot]O2 time course for a subsequent sub-[theta]L bout, it significantly speeds the [Vdot]O2 response to a subsequent supra-[theta]L bout (Gausche, Harmon, Lamarra & Whipp, 1989; Gerbino, Ward & Whipp, 1996). These investigators proposed that this speeding was a result of improved muscle perfusion during the exercise transient, possibly related to the residual metabolic acidaemia still present at the start of the subsequent exercise bout. To determine whether speeding of the [Vdot]O2 kinetics could also be induced by a bout of prior high-intensity exercise performed at a remote site (e.g. the arms), subjects each performed two 6 min bouts of high-intensity cycling (leg exercise: LE) at a work rate equivalent to 50 % of ‘[Delta]LE’ (the difference between maximum [Vdot]O2,LE and [theta]L,LE). On one occasion this was preceded by a 6 min period of cycling at 50 % [Delta]LE and, on another, by a similar period of arm-crank exercise (arm exercise: AE) at 50 % [Delta]AE; in each case, the work bouts were separated by 6 min of unloaded pedalling. Pulmonary gas exchange variables were derived breath-by-breath. During unloaded pedalling and at minute 6 of each work bout, arterialized venous blood samples were drawn from the dorsum of the heated hand or at the wrist for analysis of pH, lactate, pyruvate, noradrenaline (NAdr), adrenaline (Adr), and potassium (K+). The difference in [Vdot]O2 between minute 6 and 3 of each work bout ([Delta][Vdot]O2,[6-3]) and the 'partial' O2 deficit (O2 Def) provided indices of the slow phase of [Vdot]O2 kinetics. The initial AE and LE bouts resulted in similar degrees of metabolic (lactic) acidaemia; the residual acidaemia at the end of the subsequent 6 min recovery phase was also similar for the two protocols, as were [K+], [Adr] and [NAdr]. The subsequent LE bouts were associated with reductions in both [Delta][Vdot]O2,[6-3] and O2 Def, relative to control, with the effect being more marked when the work was preceded by a prior LE bout than a prior AE bout: [Delta][Vdot]O2,[6-3] averaging 32 and 56 % of control, respectively, and O2 Def 71 and 81 %. Consequently, the increase in [lactate] and decrease in pH induced in this second LE bout were smaller when preceded by prior leg exercise than prior arm exercise. It is therefore concluded that while metabolic acidaemia induced at a site remote from the legs is associated with a less prominent slow phase of the [Vdot]O2 kinetics for high-intensity leg exercise, a component specific to the involved contractile units appears to exert the dominant effect. The mechanisms underlying this response are, however, presently uncertain.

When subject to a transmural pressure gradient resistance arteries develop a spontaneous, intrinsically initiated contraction which varies according to the pressure stimulus and occurs in the absence of vasoconstrictor agonists. Such pressure-dependent active changes in vascular tone are indicative of the vascular myogenic response and contribute to autoregulation and the setting of total peripheral resistance and hence blood pressure regulation. The myogenic behaviour of blood vessels provides the background tone upon which other vasomotor influences act. Hypertension is associated with a raised vascular resistance and in this article the evidence for increased myogenic activity contributing to the raised vascular resistance is reviewed. Although there are some cases that provide evidence for exaggerated myogenic responsiveness in resistance arteries taken from hypertensive animals it is not possible to conclude that enhanced myogenic contractile responses within normal pressure ranges contribute to the raised total peripheral resistance. However, the myogenic tone of the resistance arteries of the various vascular beds is subject to differing modulatory influences in hypertensive animals and their normotensive controls which may contribute to the aetiology of hypertension. Experimental Physiology (2002) 87.5, 527-534.

Multiphoton microscopy is based on the simultaneous absorption of two photons emitted by a pulsed infrared laser source. In this technique, the excitation is restricted to a very small focus and thus results in optical sectioning a priori without the need of a confocal aperture. Multiphoton microscopy was introduced in live cell imaging as an alternative to confocal microscopy due to its superior qualities, such as the deep penetration depth, the reduced photodamage and the lack of out-of-focus bleaching. However, during the past years, examinations revealed severe limitations to the initial expectations. In the focal plane, photodamage and photobleaching can be worse than in single photon microscopy. However, studies showed that with low excitation intensity and by special technical adaptations photodamage could be avoided successfully. For functional biological imaging, multiphoton excitation provides an excellent tool such as the release of caged compounds in a diffraction-limited volume combined with multiphoton or confocal imaging.

We compared the kinetics of oxygen uptake ([Vdot]O2) and phosphocreatine (PCr) during the adjustment to and recovery from plantar flexion exercise in moderately active older (n = 10, 66·9 years) and younger (n = 10, 27·5 years) individuals. [Vdot]O2 kinetics were similar in the two groups, with time constants ([tau]) averaging 46·3 ± 10·2 s (younger, on-transient), 38·1 ± 14·4 s (younger, off-transient), 46·3 ± 17·8 (older, on-transient) and 40·7 ± 19·2 s (older, off-transient). These were similar to corresponding PCr kinetics, measured by 31P nuclear magnetic resonance spectroscopy, which averaged 50·6 ± 24·0 s (younger, on-transient), 42·0 ± 16·1 s (younger, off-transient), 39·8 ± 22·0 s (older, on-transient) and 37·6 ± 21·6 s (older, off-transient). On-transient [tau] values for [Vdot]O2and PCr were correlated, for combined groups (r = 0·53; P = 0·015). We conclude that: (1) [Vdot]O2 and PCr kinetics during exercise of a muscle group accustomed to daily activity are not compromised in physically active older humans, and (2) PCr kinetics reflect the kinetics of muscle O2 consumption, and are expressed at the lung ([Vdot]O2 kinetics) after a transit delay.

This study examined the relationship between muscle recruitment patterns using surface electromyography (EMG) and the excess O2 uptake (ExV˙O2) that accompanies slow (SR, 8 W min-1) but not fast (FR, 64 W min-1) ramp increases in work rate (WR) during exercise on a cycle ergometer. Nine subjects (2 females) participated in this study (25 ± 2 years, ± S.E.M.). EMG was obtained from the vastus lateralis and medialis and analysed in the time (root mean square, RMS) and frequency (median power frequency, MDPF) domain. Results for each muscle were averaged to provide an overall response and expressed relative to a maximal voluntary contraction (%MVC). ΔV˙O2/ΔWR was calculated for exercise below (S1) and above (S2) the lactate threshold (LT) using linear regression. The increase in RMS relative to the increase in WR for exercise below the LT (ΔRMS/ΔWR-S1) was determined using linear regression. Due to non-linearities in RMS above the LT, ΔRMS/ΔWR-S2 is reported as the difference in RMS (ΔRMS) and the difference in WR (ΔWR) at end-exercise and the LT. SR was associated with a higher (P < 0.05) ΔV˙O2/ΔWR (S1, 9.3 ± 0.3 ml min-1 W-1; S2, 12.5 ± 0.6 ml min-1 W-1) than FR (S1, 8.5 ± 0.4 ml min-1 W-1; S2, 7.9 ± 0.4 ml min-1 W-1) but a similar ΔRMS/ΔWR-S1 (SR, 0.11 ± 0.01% W-1; FR, 0.10 ± 0.01 % W-1). ExV˙O2 was greater (P < 0.05) in SR (3.6 ± 0.7 l) than FR (-0.7 ± 0.4 l) but was not associated with a difference in either ΔRMS/ΔWR-S2 (SR, 0.14 ± 0.01% W-1; FR, 15 ± 0.02 % W-1) or MDPF (SR, 2.6 ± 5.9 %; FR, -15.4 ± 4.5 %). The close matching between power output and RMS during SR and FR suggests that the ExV˙O2 of heavy exercise is not associated with the recruitment of additional motor units since ExV˙O2 was observed during SR only. Compared to the progressive decrease in MDPF observed during FR, the MDPF remained relatively constant during SR suggesting that either (i) there was no appreciable recruitment of the less efficient type II muscle fibres, at least in addition to those recruited initially at the onset of exercise, or (ii) the decrease in MDPF associated with fatigue was offset by the addition of a higher frequency of type II fibres recruited to replace the fatigued motor units. Experimental Physiology (2002) 87.1, 91-100.