The neurohypophysial hormone vasopressin contributes to control of urine output and, while urine flow shows a clear daily rhythm, there has been debate as to whether this is true of neurohypophysial hormones. A study was performed on fifteen adult males, with a mean age of 25 years, over a 24 h period, nine blood samples being taken at regular intervals for the determination of neurohypophysial hormones and indices of fluid balance. Samples were taken via an indwelling cannula so that sleep was undisturbed. A daily variation in the plasma concentrations of oxytocin and vasopressin was demonstrated with concentrations reaching a nadir in the late afternoon. Concentrations of both hormones peaked at 02.00 h. Vasopressin concentrations were inversely correlated with packed cell volume, indicating that the altered hormone release was affecting fluid retention. Consistent with this was the observation that the relationship of plasma osmolality to vasopressin depended on the time of day. To determine the effect of ageing, a similar study was performed on nine healthy elderly subjects with a mean age of 70 years. The nocturnal peak of vasopressin was markedly attenuated, while oxytocin release was similar to that in the younger group. These observations confirm the existence of a daily rhythm in the plasma concentrations of neurohypophysial hormones and indicate that the amplitude of the vasopressin change decreases with age.

The purpose of this study was to determine the effect of baroreceptor unloading on the sensitivity of the cardiovagal and sympathetic arms of the baroreflex during upright posture. Beat-by-beat R-R interval, arterial blood pressure and cardiac output (Doppler ultrasound), as well as muscle sympathetic nerve activity (MSNA) were recorded during periods in supine (Supine) and 60 deg head-up tilt (HUT) positions (n = 8 volunteers). Cardiovagal baroreflex sensitivity (BRS) was measured by the spontaneous sequence analysis method using systolic blood pressure and R-R interval, while sympathetic BRS was determined using the slope of the linear relationship between decreasing segments of diastolic blood pressure (DBP) and corresponding increases in MSNA. On changing to HUT, mean R-R interval and cardiac output decreased, while mean measures of MSNA, DBP and total peripheral resistance increased (P < 0.05). Cardiovagal BRS decreased from Supine to 60 deg HUT (19 ± 2 ms mmHg-1 versus 7.6 ± 1.2 ms mmHg-1; P < 0.01). In contrast, sympathetic BRS increased from -6.1 ± 1.4 a.u. mmHg-1 in Supine to -14 ± 2 a.u. mmHg-1 in HUT (P < 0.01). Thus, HUT produced differential effects on cardiac versus sympathetic BRS. The data suggest that dynamic baroreflex-mediated cardiovascular control is dominated by sympathetic control during baroreceptor unloading. Experimental Physiology (2003) 88.6, 769-774.

In both medical research and diagnostics characterization of biological tissue on the cellular level relies on high-resolution optical microscopy. In most cases, however, tissue is excised for microscopic investigation, in part because conventional microscopes are bulky instruments. Imaging of cells in the intact living organism has been difficult. Over the last decade several groups have developed miniature confocal microscopes that use fibre optics to deliver light to the specimen and to measure either reflected or excited fluorescence light. In addition, two-photon excitation recently has been employed in a small portable ‘fibrescope’. A potential clinical application of these microscope probes is their endoscopic use for optical biopsy of inner organs or guidance of conventional biopsy. As a mobile research tool they may permit imaging of neuronal activity in the brain of awake, behaving animals. Here, we review technological approaches to build miniaturized fluorescence microscopes and discuss their potential applications.

Orthostatic stress, including standing, head-up tilting and lower body suction, results in increases in peripheral vascular resistance but little or no change in mean arterial pressure. This study was undertaken to determine whether the sensitivity of the carotid baroreceptor reflex was enhanced during conditions of decreased venous return. We studied eight healthy subjects and determined responses of pulse interval (ECG) and forearm vascular resistance (mean finger blood pressure divided by Doppler estimate of brachial artery blood velocity) to graded increases and decreases in carotid transmural pressure, effected by a neck suction/pressure device. Responses were determined with and without the application of lower body negative pressure (LBNP) at -40 mmHg. Stimulus-response curves were determined as the responses to graded neck pressure changes and the differential of this provided estimates of reflex sensitivity. Changes in carotid transmural pressure caused graded changes in R-R interval and vascular resistance. The cardiac responses were unaffected by LBNP. Vascular resistance responses, however, were significantly enhanced during LBNP and the peak gain of the reflex was increased from 1.2 ± 0.3 (mean ± S.E.M.) to 2.2 ± 0.3 units (P < 0.05). The increased baroreflex gain may contribute to maintenance of blood pressure during orthostatic stress and limit the pressure decreases during prolonged periods of such stress. Experimental Physiology (2001) 86.5, 677-681.

Gender-based differences in cardiovascular mortality may be due to a cardio-protective effect of oestrogens on the myocardium. However, mRNA expression of oestrogen receptors in myocardial tissue of the adult heart has yet to be demonstrated. Furthermore, a calcium antagonistic action of 17[beta]-oestradiol on myocardial tissue has been discussed. Therefore, two subjects were investigated in atrial myocytes of the human, and ventricular myocytes of guinea-pig and rat in this study. (1) Are oestrogen receptors expressed in adult myocardial cells? (2) Is there an influence of oestrogens on the L-type calcium current of cardiac myocytes? Expression of oestrogen receptors was investigated by reverse polymerase chain reaction. L-type calcium current was usually measured by the patch-clamp technique in whole-cell recording mode under selective recording conditions, i.e. overlapping currents were blocked. One series of experiments was performed in perforated patch configuration to avoid internal perfusion. 17[beta]-Oestradiol inhibited L-type calcium current reversibly in all three species. At 10-5 M, the inhibition was 15-20 %. This inhibition was independent of the sex and the species. A full concentration-response curve of 17[beta]-oestradiol on basal L-type current was recorded from female guinea-pig myocytes. The inhibition increased from 2 % at 10-7 M to about 30 % at 10-4 M 17[beta]-oestradiol. The values could be fitted by a sum of two sigmoidal functions with log EC50 values of -6·5 and -4·9 M and Hill slopes of 2·5 for both. The specificity of the 17[beta]-oestradiol action was tested by recording the L-type current in the presence of 17[alpha]-oestradiol and oestrone. 17[alpha]-Oestradiol also inhibited the current, but with a maximal inhibition of only 17 %. The concentration-response curve could be fitted by a single sigmoidal function (log EC50 -6·3 M; Hill slope 0·55). Oestrone did not influence the current at all. The decrease in L-type current after the application of 17[beta]-oestradiol via a rapid perfusion system developed with a time constant of 3·4 s, which was in the same range as that for the influence of isoprenaline. The isoprenaline-stimulated L-type current was much more susceptible to the inhibition by 17[beta]-oestradiol, i.e. in pre-stimulated cells (1) the inhibitory effect is significantly higher (e.g. at 10-5 M, inhibition was 36·3 % compared with 11·2 % in untreated cells) and (2) an inhibitory effect can be seen with oestradiol concentrations as low as 10-9 M. Although the concentrations needed to gain a calcium antagonistic influence on the basal current were much too high to explain a cardio-protective influence of oestrogens, the presence of oestrogen receptors in cardiac myocytes of all three species, together with the shift in concentration dependence following pre-stimulation by isoprenaline, suggest that myocytes are a potential target for oestrogen.

The contractility of the human uterus is under the fine control of a variety of interacting bioactive agents. During labour, the excitability of the uterus is drastically transformed in comparison with the non-labour state and is manifest at the membrane level via the acivity of uterine ion channels. This article reviews the contribution of potassium (K+) channels to human uterine excitability. Experimental Physiology (2001) 86.2, 255-264.

In 48 conscious resting subjects we examined the temporal coupling of heart beat timing and the onset of inspiration (cardioventilatory coupling), and the relationship between coupling and spectral indices of autonomic function. Using the proportional Shannon entropy (SHα) of the RI-1 interval (interval between inspiration and the preceding ECG R wave) as a measure of coupling we detected statistically significant coupling in 32 of the 48 subjects. This was confirmed by visual inspection of time series plots of RI intervals, in which coupling was evident as horizontal banding. Coupling resulted in a significant preference for whole number heart rate/respiratory frequency ratios. The strongest coupling was associated with low ventilatory frequency and high heart rate variability in the high (0.15-0.40 Hz) and low (0.04-0.15 Hz) frequency ranges, but was not related to blood pressure variability, or to a spectral measure of baroreflex sensitivity (α-index, low frequency range). There was no difference in coupling strength between males and females. We have previously described cardioventilatory coupling in spontaneously breathing anaesthetised subjects. The current study extends those observations by demonstrating that the qualitative features of coupling seen during anaesthesia are also observed in the conscious state. We conclude that the role of coupling in normal physiological respiratory control needs to be more widely explored. Experimental Physiology (2003) 88.6, 775-782.

Small size at birth has been associated with increased blood pressure in adult men and women. In rats, isocaloric protein restriction reduces fetal growth and increases systolic blood pressure in adult offspring. Balanced maternal undernutrition in the rat also increases adult blood pressure, but not consistently. The aim of this study was to determine the effect of moderate balanced maternal undernutrition (85% of ad libitum intake from 4 weeks before, and throughout pregnancy) on blood pressure of adult offspring in the guinea pig, a species that is relatively mature at birth. Blood pressure was measured in chronically catheterised offspring of ad libitum fed or feed-restricted mothers, at 3 months of age (young adult). Maternal feed restriction reduced birth weight (−17%) and increased systolic blood pressure (+9%, P < 0.03) in young adult male offspring. In offspring of ad libitum fed and feed-restricted mothers, combined data showed that systolic blood pressure and mean arterial pressure correlated negatively with head width at birth (P = 0.02 and P = 0.04, respectively, n = 28). Systolic blood pressure also correlated negatively with birth weight and the ratio birth weight/birth length, but only in offspring of ad libitum fed mothers (P = 0.04 and P = 0.03, respectively, n = 22). The effect of maternal feed restriction on systolic blood pressure in male offspring was not significant when adjusted for these measures of size at birth. Thus, moderate balanced undernutrition in the guinea pig increases systolic blood pressure in young adult male offspring; however, these effects may be mediated, at least in part, through effects on fetal growth.

The effect of added respiratory work on leg muscle oxygenation during constant-load cycle ergometry was examined in six healthy adults. Exercise was initiated from a baseline of 20 W and increased to a power output corresponding to 90 % of the estimated lactate threshold (moderate exercise) and to a power output yielding a tolerance limit of 11.8 min (± 1.4, S.D.) (heavy exercise). Ventilation and pulmonary gas exchange were measured breath-by-breath. Profiles of leg muscle oxygenation were determined throughout the protocol using near-infrared (NIR) spectroscopy (Hamamatsu NIRO 500) with optodes aligned midway along the vastus lateralis of the dominant leg. Four conditions were tested: (i) control (Con) where the subjects breathed spontaneously throughout, (ii) controlled breathing (Con Br) where breathing frequency and tidal volume were matched to the Con profile, (iii) increased work of breathing (Resist Br) in which a resistance of 7 cmH2O l-1 s-1 was inserted into the mouthpiece assembly, and (iv) partial leg blood flow occlusion (Leg Occl), where muscle perfusion was reduced by inflating a pressure cuff (~90 mmHg) around the upper right thigh. During Resist Br and Leg Occl, subjects controlled their breathing pattern to reproduce the ventilatory profile of Con. An ~3 min period with respiratory resistance or pressure cuff was introduced ~4 min after exercise onset. NIR spectroscopy data for reduced haemoglobin-myoglobin (Δ[Hb]) were extracted from the continuous display at specific times prior to, during and after removal of the resistance or pressure cuff. While the Δ[Hb] increased during moderate- and heavy-intensity exercise, there was no additional increase in Δ[Hb] with Resist Br. In contrast, Δ[Hb] increased further with Leg Occl, reflecting increased muscle O2 extraction during the period of reduced muscle blood flow. In conclusion, increasing the work of breathing did not increase leg muscle deoxygenation during heavy exercise. Assuming that leg muscle O2 consumption did not decrease, this implies that leg blood flow was not reduced consequent to a redistribution of flow away from the working leg muscle. Experimental Physiology (2002) 87.5, 601-611.

The activation of cardiovascular reflexes for postural adaptation questions whether, in healthy humans, the central blood volume is optimised to support the upright position. A functional definition of an 'optimal circulating volume' that provides the heart with enough central blood volume to establish a maximal cardiac output (CO) and mixed venous oxygen saturation (Sv,O2) at rest was evaluated in nine healthy subjects. Preload to the heart was varied by passively changing the body position from 70 deg head-up to 20 deg head-down tilt. The Sv,O2 was compared with simultaneously measured estimates of CO by computer-controlled thermodilution. The CO was in the range 8.7-3.8 l min-1 and Sv,O2 was in the range 79-58 %. Neither CO (median 6.0 (range 5.3-8.7) l min-1) nor Sv,O2 (mean ± S.D. 73.6 ± 2.6 %) changed from the supine to the 20 deg head-down position. During sustained 70 deg head-up tilt, Sv,O2 decreased to 64 ± 4 % together with a decline in CO to 4.7 (3.9-5.6) l min-1 (P < 0.05). Under conditions of varying tilt angles, a change in CO is paralleled by concordant changes in Sv,O2. Maximal values for CO and Sv,O2 during supine rest suggest that the horizontal position provides for an 'optimal' central blood volume. Experimental Physiology (2003) 88.5, 611-616.

The cellular mechanisms that underlie the initiation and propagation of the peristaltic contractions, which transport urine from the kidney to the bladder for storage, remain little understood. Extracellular and intracellular microelectrode recordings have identified two populations of smooth muscle cells as well as a population of renal interstitial cells (RICs) that all display spontaneous electrical activity. By analogy with the heart it has been proposed that atypical smooth muscle cells, preferentially located in the very proximal regions of the renal pelvis, generate the essential pacemaker signal. These pacemaker potentials propagate to neighbouring typical smooth muscle cells or RICs to trigger action potential discharge. These action potentials then propagate distally to trigger other bundles of typical smooth muscle cells. The frequency of action potential discharge and contraction decreases as the relative number of RICs and atypical smooth muscle cells compared to typical smooth muscle cells decreases with distance from the renal fornix. It is clear that functional capsaicin-sensitive sensory afferents and the endogenous release of both tachykinins and prostaglandins are essential in the maintenance of normal peristalsis, as well as in monitoring and responding to any chemical or mechanical stimulation. However, the cellular mechanisms underlying the action of these endogenously-released agents remain to be elucidated. Experimental Physiology (2002) 87.2, 129-146.

The affective responses to pain arising from deep somatic and visceral tissues differ markedly from those evoked by brief cutaneous insults. Deep pain evokes passive emotional coping that includes quiescence and vasodepression. In contrast, cutaneous pain evokes an active emotional coping: the fight or flight response. There is now considerable evidence to support the notion that nociceptive inputs arising from different peripheral domains drive the different functional columns of the periaqueductal grey (PAG) that co-ordinate either active or passive coping strategies. Nociceptive inputs from deep structures drive neurones in the ventrolateral columns that co-ordinate passive emotional coping whereas brief cutaneous insults activate the dorsolateral/lateral columns that co-ordinate active coping strategies. An emerging concept, as presented in the preceding article by Keay & Bandler, is that it is the behavioural significance of the nociceptive input, rather than its organ of origin per se, that determines the characteristics of the affective response. These authors provide evidence that brief, escapable stimuli activate neurones in the dorsolateral/lateral columns of the PAG and that inescapable, persistent pain, irrespective of its organ of origin, activates the ventrolateral column. This review will present recent evidence that differential representation of escapable and inescapable pain in the PAG extends to distinct representations of 'first' and 'second' pain, as indicated by the columnar distribution of neurones activated by inputs from Aδ- and C-nociceptors. Furthermore, the functional organisation of projections from circumscribed regions of the hypothalamus to the different columns of the PAG indicates that the behavioural significance of the pain signal is represented in brain regions other than the PAG. Experimental Physiology (2002) 87.2, 281-286.

We hypothesised that maternal uterine artery vascular dysfunction could contribute to cardiovascular dysfunction in offspring of rats fed a diet rich in fat. Sprague-Dawley rats were fed for 10 days prior to pregnancy and throughout gestation either: (a) a control breeding diet, or (b) the same diet supplemented with 20 % w/w lard, vitamins, essential micronutrients and protein to control values. At 20 days gestation vascular function was assessed in uterine arteries and third-order mesenteric arteries. Vascular reactivity in response to application of potassium, noradrenaline, the thromboxane analogue U46619, acetylcholine and nitric oxide was assessed. Maternal plasma concentrations of factors likely to contribute to endothelial dysfunction were measured. Maximum acetylcholine-induced relaxation was impaired in the mesenteric arteries of the lard-fed dams (max % relaxation: lard-fed, 69.7 ± 6.48; control, 85.37 ± 2.69, P = 0.03). Uterine artery vascular function was similar in the two groups (max % acetylcholine-induced relaxation: lard-fed, 73.7 ± 4.01; control, 77.5 ± 4.72, P = 0.98). Concentrations of plasma lipids, 8-epi-PGF2α and leptin were normal, whereas insulin and corticosterone concentrations were raised in the lard-fed group (insulin (ng ml-1): lard-fed, 8.04 ± 0.47; control, 1.35 ± 0.37, P < 0.0001; corticosterone (ng ml-1): lard-fed, 1164.0 ± 170.9; control, 541.9 ± 96.3, P = 0.005). Fetal and placental weights were reduced in lard-fed dams (fetus (g): lard-fed, 4.27 ± 0.38; control, 2.96 ± 0.40, P = 0.025; placenta (g): lard-fed, 0.72 ± 0.06; control, 0.57 ± 0.04, P = 0.05). Cardiovascular dysfunction in offspring is not associated with reduced uterine artery endothelial function but is associated with activation of the hypothalamic-pituitary-adrenal axis, hyperinsulinaemia and fetoplacental growth retardation. Experimental Physiology (2003) 88.3, 389-398.

Force (and power)-velocity characteristics were determined at different stimulation frequencies in in situ rat muscle with nerve stimulation at 36¡C. In isometric contractions (duration, 150 ms), maximal force is generated at ~120 Hz. In contrast, in the high velocity (250 mm s-1) shortening contractions, frequencies of ~400 Hz were needed to obtain maximal dynamic force, while 120 Hz elicited only ~26 % of the maximum. At the highest velocity measured, power production was significantly different (P < 0·05) among frequencies of 80, 120, 200 and 400 Hz, suggesting that maximal shortening velocity should be assessed using very high stimulation frequencies. However, the results further indicate that lower frequencies may be adequate in exercise studies that investigate fatigue and changes in power output during series of repetitive contractions.

Force-velocity data at different temperatures (range, 10-35¡C) from intact fibre bundles are analysed to determine the temperature dependence of the maximal mechanical power output of fast and slow rat muscles. At 35¡C, the maximal mechanical power was [similar]250 kW m-3 (= 250 µW mm-3) in fast (probably an underestimate) and [similar]100 kW m-3 in slow muscle. Within the more physiological temperature range (25-35¡C), the temperature coefficient (Q10) of maximum power was 2-2·5. In both muscles, the maximal power at 10¡C was only about 3-5 % of that at 35¡C, the decrease being particularly pronounced at temperatures below 20¡C (Q10 of 5-7).

Understanding the relationship of the structure of organs to their function is a key component of integrative physiological research. The structure of the organs of the body is not constant but changes, both during growth and development and under conditions of sustained stress (e.g. high altitude exposure and disease). Recently, powerful new techniques have become available in molecular biology, which promise to provide novel insights into the mechanisms and consequences of these altered structure–function relationships. Conventionally structure–function relationships are studied by microscopic examination of tissue sections. However, drawing conclusions about the three-dimensional structure of an organ based on this two-dimensional information frequently leads to serious errors. The techniques of stereology allow precise and accurate quantification of structural features within three-dimensional organs that relate in a meaningful way to integrated function. For example, knowledge of changes in the total surface area of the capillary endothelium in an organ can be related directly to changes in fluid filtration and permeability, or knowledge of total vessel length and mean radius allows deductions about vascular resistance. Confocal microscopy adds enormously to the power of stereological approaches. It reduces the difficulties and labour involved in obtaining suitable images. Moreover, when used in conjunction with new analytical software, it allows convenient application of stereology to small samples and those in which it is essential to maintain a specific orientation for interpretation. The information obtained will allow us to examine in a quantitative manner the altered structure–function relationships produced by manipulation of single genes and regulatory pathways in whole organisms.

The present study examined the hypothesis that the antagonistic ankle dorsiflexor coactivation level during maximum isometric voluntary plantarflexion (MVC) is a function of ankle angle. Six male subjects generated plantarflexion and dorsiflexion MVC trials at ankle angles of -15 deg (dorsiflexed direction), 0 deg (neutral position), +15 deg (plantarflexed direction) and +30 deg having the knee flexed at an angle of 90 deg. In all contractions surface EMG measurements were taken from tibialis anterior and soleus which were considered representative muscles of all dorsiflexors and plantarflexors, respectively. Antagonistic dorsiflexor coactivation was expressed as normalized EMG and moment. Calculations of the antagonistic dorsiflexor moment were based on the tibialis anterior EMG-dorsiflexor moment relationship from contractions at 50, 40, 30, 20 and 10 % of the dorsiflexion MVC moment. In both legs dorsiflexor coactivation level followed an open U-shaped pattern as a function of ankle angle. Differences of 9 and 14 % (P < 0·05) were found in the measured net plantarflexion MVC moment between legs at ankle angles of -15 and +30 deg, respectively. No difference (P > 0·05) was found in the calf circumference between legs. Differences were found in the antagonistic dorsiflexor coactivation between legs at ankle angles of -15 and +30 deg. In the weaker leg the antagonistic EMG measurements were higher by 100 and 45 % (P < 0·01) and the estimated antagonistic moments were higher by 70 and 43 % (P < 0·01) compared with the weaker leg at -15 and +30 deg, respectively. This finding was associated with a decreased range of motion (ROM) in the weaker leg (14 %, P < 0·01), such that no difference (P > 0·05) was found in dorsiflexor antagonistic coactivation between legs at end-range ankle angles. The findings of the study (i) have to be taken into consideration when estimating musculoskeletal loads in the lower extremity, (ii) imply that stretching training can result in a stronger plantarflexion at end-range ankle angles through inhibition of the dorsiflexors, and (iii) imply a neural drive inadequacy during a plantarflexion MVC at end-range angles.

To study the effect of temperature on muscle metabolism during submaximal exercise, six endurance-trained men had one thigh warmed and the other cooled for 40 min prior to exercise using water-perfused cuffs. One cuff was perfused with water at 50-55¡C (HL) with the other being perfused with water at 0¡C (CL). With the cuffs still in position, subjects performed cycling exercise for 20 min at a work load corresponding to 70 % VO2,peak (where VO2,peak is peak pulmonary oxygen uptake) in comfortable ambient conditions (20-22¡C). Muscle biopsies were obtained prior to and following exercise and forearm venous blood was collected prior to and throughout the exercise period. Muscle temperature (Tmus) was not different prior to treatment, but treatment resulted in a large difference in pre-exercise Tmus (difference = 6á9 ± 0á9¡C; P < 0á01). Although this difference was reduced following exercise, it was nonetheless significant (difference = 0á4 ± 0á1¡C; P < 0á05). Intramuscular [ATP] was not affected by either exercise or muscle temperature. [Phosphocreatine] decreased (P < 0á01) and [creatine] increased (P < 0á01) with exercise but were not different when comparing HL with CL. Muscle lactate concentration was not different prior to treatment nor following exercise when comparing HL with CL. Muscle glycogen concentration was not different when comparing the trials before treatment, but the post-exercise value was lower (P < 0á05) in HL compared with CL. Thus, net muscle glycogen use was greater during exercise with heating (208 ± 23 vs. 118 ± 22 mmol kg-1 for HL and CL, respectively; P < 0á05). These data demonstrate that muscle glycogen use is augmented by increases in intramuscular temperature despite no differences in high energy phosphagen metabolism being observed when comparing treatments. This suggests that the increase in carbohydrate utilization occurred as a direct effect of an elevated muscle temperature and was not secondary to allosteric activation of enzymes mediated by a reduced ATP content.

We hypothesised that the observed acceleration in the kinetics of exercise on-transient oxygen uptake (V˙O2) of five older humans (77 ± 7 years (mean ± S.D.) following 9 weeks of single-leg endurance exercise training was due to adaptations at the level of the muscle cell. Prior to, and following training, subjects performed constant-load single-limb knee extension exercise. Following training V˙O2 kinetics (phase 2, τ) were accelerated in the trained leg (week 0, 92 ± 44 s; week 9, 48 ± 22 s) and unchanged in the untrained leg (week 0, 104 ± 43 s; week 9, 126 ± 35 s). The kinetics of mean blood velocity in the femoral artery were faster than the kinetics of V˙O2, but were unchanged in both the trained (week 0, 19 ± 10 s; week 9, 26 ± 11 s) and untrained leg (week 0, 20 ± 18 s; week 9, 18 ± 10 s). Maximal citrate synthase activity, measured from biopsies of the vastus lateralis muscle, increased (P < 0.05) in the trained leg (week 0, 6.7 ± 2.0 µmol (g wet wt)-1 min-1; week 9, 11.4 ± 3.6 µmol (g wet wt)-1 min-1) but was unchanged in the untrained leg (week 0, 5.9 ± 0.5 µmol (g wet wt)-1 min-1; week 9, 7.9 ± 1.9 µmol (g wet wt)-1 min-1). These data suggest that the acceleration of V˙O2 kinetics was due to an improved rate of O2 utilisation by the muscle, but was not a result of increased O2 delivery. Experimental Physiology (2001) 86.5, 659-665.

Thermoregulation in control subjects and cold-adapted winter swimmers was examined during 1 h of cold water immersion (13 °C). It was found that the thermoregulatory functions of winter swimmers differ from those of non-cold-adapted subjects. As evident from the relationship between rectal temperature and the magnitude of cold thermogenesis, in controls a significant part of cold thermogenesis during the early phase of cooling was induced by changes in peripheral temperature input, while in the late phase of cooling it was the central temperature input which was mainly engaged in induction of cold thermogenesis. In winter swimmers the magnitude of cold thermogenesis was solely related to changes in rectal temperature, indicating the predominance of the central temperature input in activation of heat production mechanisms. The thermoregulatory threshold for induction of cold thermogenesis was lowered (by 0.34 °C), but the apparent hypothalamic thermosensitivity was the same as in non-cold-adapted subjects. These differences are indicative of adaptation of thermoregulatory control centres. Additionally, the activity of thermoregulatory effectors was also changed. Shivering was induced later during cooling (after 40 min) in winter swimmers than in controls, which suggests an important participation of non-shivering thermogenesis in the early thermogenic response. Winter swimmers also showed bradycardia and a greater reduction in plasma volume during cooling. The data indirectly indicate restriction of heat loss from the body. Only a non-significant increase in quantity of subcutaneous fat was observed in winter swimmers. Thus, winter swimmers were able to survive a significantly greater temperature gradient between body and environment than non-cold-adapted subjects by modifying the sensory functions of hypothalamic thermoregulatory centres to lower heat loss and produce less heat during cold exposure. Additionally, the capacity of the total cold thermogenesis due to potentiation of non-shivering heat production was also increased. Heat produced due to thermogenic action of adrenaline may represent more than a quarter of the total cold thermogenesis. In conclusion, the data suggest that winter swimmers exhibit metabolic, hypothermic and insulative types of cold adaptation. Experimental Physiology (2000) 85.3, 321-326.