Changes in the composition of fibre types and the capillary supply of skeletal muscle (tibialis anterior) were quantified in rats and hamsters subjected to 8-10 weeks of cold exposure and reduced photoperiod (10 °C, 1 h light-23 h dark). Muscle mass decreased in both species (by 12 % and 17 %, respectively). Following acclimation to cold there were no specific changes in fibre cross-sectional area (FCSA) in rats, whereas in hamsters there was a substantial atrophy of Type II, but not Type I fibres. In rat muscle there was little difference between the two groups in average capillary to fibre ratio (C:F) (1.76 ± 0.15, normothermia, N; 1.69 ± 0.05, hypothermia, H) and average capillary density (CD) (188 ± 14 mm-2, N; 201 ± 12 mm-2, H). Similarly, the average C:F was unaltered in hamsters (2.75 ± 0.11, N; 2.72 ± 0.15, H), although the 30 % smaller fibre size observed with hypothermia resulted in a corresponding increase in average CD, to 1539 ± 80 mm-2 (P < 0.01). However, there was a coordinated regional adaptation to cold exposure in hamsters resulting in capillary rarefaction in the glycolytic cortex and angiogenesis in the oxidative core. Following acclimation of rats to cold there was a reduction in the supply area of individual vessels (capillary domain), particularly in the cortex (9310, N; 8938 µm2, H; P < 0.05). In contrast, hypothermic hamsters showed only a small decrease in mean domain area in the cortex (948 µm2, N; 846 µm2, H; n.s.) but a marked reduction in the core (871 µm2, N; 604 µm2, H; P < 0.01). Rats showed little or no change in local capillary supply (LCFR) to fast fibres on acclimation to cold, while in hamsters the LCFR of Type IIb fibres showed a decrease in the cortex (2.7, N; 2.3, H) and an increase in the core (3.0, N; 3.3, H) during acclimation to cold. These data suggest that during a simulated onset of winter rats maintain FCSA and capillary supply as part of an avoidance strategy, whereas hamsters increase muscle capillarity in part as a consequence of disuse atrophy. Experimental Physiology (2001) 86.5, 629-639.

Genetically modified mice have become an invaluable tool in modern biomedical and basic research. This review provides an overview of knockout and transgenic mice studied with regard to their cutaneous wound healing properties. In addition, several gene transfer studies are briefly introduced, which have further highlighted our knowledge on individual gene function in wound healing

We have investigated the effect of acidosis on the ECG in isolated rat heart to determine whether acidosis has marked effects on the ECG, and have used pharmacological agents to investigate possible mechanisms whereby acidosis alters the ECG. Acidosis produced a marked decrease in heart rate and an increase in P-R interval with little apparent effect on the duration of the QRS complex. The effects of acidosis did not appear to be due to acidosis-induced changes in transmitter release from severed autonomic nerve terminals within the heart. Experimental Physiology (2001) 86.1, 27-31.

Primary thoracic blast injury causes a triad of bradycardia, hypotension and apnoea mediated in part via a vagal reflex. Blast casualties may also suffer blood loss, and the response to progressive simple haemorrhage is biphasic: an initial tachycardia followed by a vagally mediated reflex bradycardia which can be attenuated by μ opioid agonists. The aims of this study were to determine the effects of thoracic blast injury on the response to subsequent haemorrhage, and the effects of morphine, administered after blast, on the response to blood loss. Male Wistar rats, terminally anaesthetised with alphadolone–alphaxolone (19–21 mg kg−1 h−1 I.V.), were allocated randomly to one of three groups: Group I, sham blast; Group II, thoracic blast; Group III, thoracic blast plus morphine (0.5 mg kg−1 I.V. given 5 min after blast). Blast (Groups II and III) resulted in significant (P<0.05, ANOVA) bradycardia, hypotension and apnoea. Sham blast (Group I) had no effect. Ten minutes later, haemorrhage (40% of the estimated total blood volume (BV)) in Group I produced a biphasic response comprising a tachycardia followed by a peak bradycardia after the loss of 33% BV. Arterial blood pressure did not fall significantly until the loss of 13.3% BV. In Group II the haemorrhage-induced tachycardia was absent and the bradycardia was augmented: peak bradycardia was seen after the loss of 23% BV. Mean arterial blood pressure (MBP) began to fall as soon as haemorrhage commenced and was significant after the loss of 10% BV. Morphine (Group III) prevented the haemorrhage-induced bradycardia and delayed the significant fall in MBP until the loss of 30% BV. It is concluded that the response to thoracic blast injury augments the depressor response to haemorrhage while morphine attenuates this response.

Basic fibroblast growth factor (bFGF) is a potent mitogen which induces growth of collateral vessels in ischaemic and infarcted myocardium. The effect of systemically administered bFGF on left ventricular (LV) function, myocardial hypertrophy and LV remodelling following acute myocardial infarction (MI) have not yet been fully investigated. Thirty Sprague-Dawley male rats were randomized to receive bFGF (0·5 mg) or rat albumin intraperitoneally for 1 week, beginning immediately after the induction of MI. Five animals served as controls and did not undergo any operation. Animals were killed 6 weeks after surgery and the hearts were perfused and fixed at physiological pressure. Transverse cross-sections from infarcted areas were stained with antibodies against proliferating cell nuclear antigen (PCNA) and Masson-trichrome and analysed with a coloured-image analyser for LV area (mm2), LV cavity diameter (mm), infarcted area (%), and wall thickness (mm) in infarcted and non-infarcted regions. LV area was similar in MI rats and in controls (41·7 ± 6·9 and 43·0 ± 1·5 mm2, respectively) and was significantly larger in MI bFGF-treated (MI/bFGF) animals (47·6 ± 7·1 mm2) (P = 0·023). LV cavity diameter was significantly larger in the MI group than in MI/bFGF and control animals (6·0 ± 0·8, 4·9 ± 1·4, and 4·4 ± 0·8 mm, respectively, P = 0·018). Wall thickness in the non-infarcted region was significantly smaller in MI animals (1·4 ± 0·3 mm) than in MI/bFGF animals (1·6 ± 0·4 mm) and the control group (1·6 ± 0·1 mm) (P = 0·015). The ratio between LV cavity diameter/non-MI wall thickness was higher in MI than in control and MI/bFGF groups (4·8 ± 1·6, 2·7 ± 0·6 and 3·3 ± 1·8, respectively, P = 0·03). Proliferating endothelial cells were significantly more abundant in infarcted than in normal areas in both MI and MI/bFGF groups, but with no significant differences between the groups. Intraperitoneal administration of bFGF did not cause any untoward extracardiac effects. Thus, systemic bFGF administration following acute MI in rats prevents dilatation of the LV, induces hypertrophy of the non-infarcted myocardium and exerts no untoward effects on extracardiac organs.

The deterioration of the immune system with ageing, which leads to an increased morbidity and mortality from infections, appears to be related to decreases in specific lymphocyte functions. However, the alteration of non-specific immunity is a more controversial subject. Our purpose was to investigate the age-related changes of different functions of the non-specific immune response in peritoneal macrophages (adherence to tissues, mobility directed to a chemical gradient from an infectious focus or chemotaxis, phagocytosis of foreign agents and destruction of these agents by superoxide anion production) and in lymphocytes (adherence and chemotaxis) from peritoneum, axillary lymph nodes, spleen and thymus. We used young (12 weeks), adult (22 weeks), mature (48 weeks) and old (72 weeks) female BALB/c mice. The adherence capacity of macrophages and lymphocytes was greater in adult and old mice than in young animals. The chemotaxis of macrophages showed higher values in cells from young mice than in those from adult mice, increasing again in macrophages from mature and old animals. A similar behaviour was shown by phagocytosis, which reached its highest values in old animals. Anion superoxide production increased with age and again the highest values were obtained in the oldest mice. Conversely, chemotaxis of lymphocytes was higher in the adult and mature animals than in the young and old animals. We conclude that, although there is a decrease in lymphocyte chemotaxis in old animals, the non-specific immune response of macrophages instead of decreasing, may increase in aged mice with respect to the values seen in adult mice. Experimental Physiology (2000) 85.5, 519-525.

The induction of Fos protein was used to localise hypothalamic neurones activated by noxious somatic stimulation. This was combined with retrograde transport of fluorescent latex microspheres from identified 'pressor' and 'depressor' sites in the dorsolateral/lateral or ventrolateral columns of the periaqueductal grey (PAG). Fos-positive neurones were found throughout the rostral hypothalamus. Of those neurones activated by noxious somatic stimuli that projected to the PAG all but one was retrogradely labelled from sites that included the lateral column. Only one neurone was double labelled following injection of tracer at a depressor site in the ventrolateral PAG. This is in marked contrast to visceroresponsive hypothalamic neurones, a larger proportion of which project to the PAG and which, as reported previously, preferentially target depressor sites in the ventrolateral sector. These results are discussed in relation to the roles of the anterior hypothalamus and the different functional columns of the PAG in co-ordinating autonomic and sensory functions in response to nociceptive inputs originating in different peripheral domains. Experimental Physiology (2002) 87.2, 117-122.

The aim of this study was to characterise the arrhythmogenic mechanisms involved in hypokalaemia-induced sustained ventricular fibrillation (SVF), in hypertensive rats. The hearts from rats with hypertension induced by the nitric oxide synthase inhibitor L-NAME, and age-matched normotensive controls, were perfused in Langendorff mode with oxygenated Krebs-Henseleit solution followed by a K+-deficient solution. In additional experiments, free intracellular Ca2+ concentration ([Ca2+]i) was measured using fura-2 in conjunction with an epicardial optical probe. The epicardial electrocardiogram was continuously monitored during all experiments. The gap junction protein connexin-43 and the ultrastructure of the cardiomyocytes were examined, and selected enzyme activities were measured in situ. There was a higher incidence of low-K+-induced SVF in the hearts of hypertensive compared to normotensive rats (83 % vs. 33 %, P < 0.05). Perfusion with a low-K+-containing solution lead to elevation of diastolic [Ca2+]i that was accompanied by premature beats, bigeminy, ventricular tachycardia and transient ventricular fibrillation. These events occurred earlier with increased incidence and duration in the hearts of hypertensive rats (arrhythmia scores: hypertensive, 4.9 ± 0.7; normotensive, 3.1 ± 0.1; P < 0.05), which exhibited apparent remodelling accompanied by a significant decrease in the density of connexin-43-positive gap junctions. Moreover, low-K+-related myocardial changes, including local impairment of intermyocyte junctions, ultrastructural alterations due to Ca2+ overload and intercellular uncoupling, and decreased enzyme activities were more pronounced and more dispersed in hypertensive than normotensive rats. In conclusion, nitric oxide-deficient hypertension is associated with decreased myocardial coupling at gap junctions. The further localised deterioration of junctional coupling, due to low-K+-induced Ca2+ disturbances, as well as spatial heterogeneity of myocardial alterations including interstitial fibrosis, probably provide the mechanisms for re-entry and sustaining ventricular fibrillation. Experimental Physiology (2002) 87.2, 195-205.

The strength of synaptic connections in the brain is not fixed, but can be modulated by numerous mechanisms. Traditionally, electrophysiology has been used to characterize connections between neurons. Electrophysiology typically reports the activity of populations of synapses, while most mechanisms of plasticity are thought to operate at the level of single synapses. Recently, two-photon laser scanning microscopy has enabled us to perform optical quantal analysis of individual synapses in intact brain tissue. Here we introduce the basic principle of the two-photon microscope and discuss its main differences compared to the confocal microscope. Using calcium imaging in dendritic spines as an example, we explain the advantages of simultaneous dual-dye imaging for quantitative calcium measurements and address two common problems, dye saturation and background fluorescence subtraction.

Hypoxic pulmonary vasoconstriction (HPV) may be mediated, in part, by an oxygen-sensing mechanism intrinsic to pulmonary arterial smooth muscle. It has been proposed that hypoxia inhibits a K+ conductance, which promotes membrane depolarization, subsequent activation of L-type Ca2+ channels and ultimately constriction. We have monitored hypoxia-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) of single myocytes isolated from the rat pulmonary arterial tree using microspectrofluorimetry and ratiometric measurement of indo-1 fluorescence. The basal level of [Ca2+]i was in the range 35-80 nM and cells were quiescent at rest exhibiting no spontaneous oscillations in [Ca2+]i. When the extracellular K+ concentration ([K+]o) was raised to 20 mM, the [Ca2+]i increased from [similar]60 to [similar]100 nM. This increase was abolished by nifedipine, demonstrating the presence, and need for activation, of functional voltage-gated L-type Ca2+ channels. Hypoxia (PO2 [less than or equal to] 30 mmHg; throughout) had little effect on the resting [Ca2+]i in myocytes isolated from either the main intrapulmonary artery, or its primary, secondary or tertiary branches. However, upon raising the [Ca2+]i by increasing [K+]o to 20 mM, hypoxia was found to lower [Ca2+]i, from [similar]110 to [similar]70 nM, in cells isolated from the main conduit and primary branches of the intrapulmonary artery. In marked contrast, when [Ca2+]i was raised, by increasing [K+]o to 20 mM, in myocytes isolated from secondary and tertiary branches of the intrapulmonary artery, hypoxia induced a further reversible increase in the [Ca2+]i from [similar]160 to [similar]240 nM. Neither hypoxia alone nor in combination with 20 mM K+o induced any increase in the [Ca2+]i in the presence of nifedipine. We conclude that hypoxia may modulate [Ca2+]i in rat pulmonary artery myocytes only following its elevation by a depolarizing stimulus.

In the Dahl salt-sensitive hypertensive rat, a diet containing L-arginine, the natural substrate for nitric oxide synthase, abrogates the hypertension. We postulated that nitric oxide synthase inhibition might induce a salt-sensitive form of hypertension and that this salt sensitivity might be linked to a loss of the regulatory effect of sodium ingestion on angiotensin II (Ang II) and angiotensinogen. Male Wistar-Kyoto rats were randomised to a diet containing 0.008 %, 2.2 % or 4.4 % sodium chloride and to treatment with the NO synthase inhibitor L-NAME (10 mg kg-1 day-1) in the drinking water, or drinking water alone (Controls) for 4 weeks. Blood pressure was measured by tail cuff plethysmography twice weekly. After 4 weeks, the rats were anaesthetised and truncal blood collected for determination of angiotensinogen, renin, angiotensin I (Ang I), Ang II and aldosterone concentrations as well as angiotensin-converting enzyme (ACE) activity. Systolic blood pressure increased with increasing dietary sodium intake in the L-NAME-treated rats (P < 0.05). Plasma renin and aldosterone concentrations decreased with increasing dietary sodium intake in both Control and L-NAME-treated rats. Ang I and ACE activity were unchanged by increasing dietary sodium intake. In contrast, the plasma concentration of Ang II and angiotensinogen increased with increasing dietary sodium (P < 0.05 and P < 0.005, respectively). Treatment with the Ang II receptor blocker, losartan, reversed the blood pressure increase. We conclude that treatment with L-NAME induces an increase in blood pressure that is at least in part salt sensitive. Further, the salt-sensitive component appears to be Ang II-dependent, as it was associated with increasing plasma Ang II levels and could be reversed by treatment with an Ang II receptor antagonist. Experimental Physiology (2002) 87.1, 1-8.

We have functionally expressed and identified a monocarboxylate transporter (MCT1) from rat jejunal enterocyte and we provide evidence for its basolateral localization. Poly(A)+ RNA isolated from rat jejunum was injected into Xenopus laevis oocytes and expression of a proton-lactate symporter was investigated by means of L-[14C]lactate uptake. The existence of an endogenous capacity for L-lactate transport was demonstrated; when, however, oocytes were injected with jejunal mRNA, an expressed L-lactate uptake was seen which differed from the endogenous transporter since it was significantly pH dependent. After sucrose density gradient fractionation, the highest expression of the pH-dependent lactate uptake was detected with the mRNA size fraction of about 2-3 kb in length. The substrate specificity, stereoselectivity and sensitivity to pCMBS (an organomercurial thiol reagent that modifies cysteine residues) of the expressed transport were in good agreement with results previously obtained using isolated jejunal basolateral membranes. Using the reverse transcriptase-polymerase chain reaction, the presence of mRNA coding for the MCT1 isoform was demonstrated in jejunal enterocytes. These data, together with previous results, suggest that MCT1 is a major route for lactate efflux across the basolateral membrane of rat jejunum; this is in contrast to current opinion which restricts the presence of MCT1 to the apical membrane of the whole small intestine.

This study focuses on the potential role for nitric oxide on the actions of the parasympathetic innervation to the heart. Earlier, we showed that the nitric oxide synthase (NOS) inhibitor N[omega]- nitro-L-arginine methyl ester (L-NAME) reduced the bradycardia induced by stimulation of vagal efferent motor fibres and that these effects are reversible through administration of the NOS substrate L-arginine. In the present study, we show that D-arginine does not reverse the effects of the inhibitors and confirm that they are reversed by L-arginine. Another NOS inhibitor, NG -nitro-L-arginine (L-NOARG), produced similar effects which were not reversed by L-arginine. In an examination of the effect of increasing NO availability with the NO donor sodium nitroprusside the vagally induced bradycardia was enhanced at all frequencies tested. In a separate series, the effects of NOS inhibitors and NO donors on the dromotropic actions of the vagus were examined. The NOS inhibitor L-NAME, reduced the increase in atrio-ventricular conduction delay normally induced by efferent vagal stimulation at all frequencies tested both in the 'paced' and 'unpaced' heart. Further, sodium nitroprusside enhanced this delay. Overall the study indicates that NO has an important facilitatory role on both the chronotropic and dromotropic actions of the vagus nerve on the heart and that NO may be a rate-limiting factor in the cardiac responses to vagal stimulation.

Mitochondrial diseases are a heterogeneous group of disorders caused by the impairment of the mitochondrial oxidative phosphorylation system which have been associated with various mutations of the mitochondrial DNA (mtDNA) and nuclear gene mutations. The clinical phenotypes are very diverse and the spectrum is still expanding. This review gives an overview of the principal clinical phenotypes and the molecular genetic basis of mitochondrial disorders identified so far. Experimental Physiology (2003) 88.1, 155-166.

Uptakes of oxygen, glucose and lactate by the gravid uterus, fetus and uteroplacental tissues were measured in chronically catheterized pregnant ponies and their fetuses at mid- and late gestation (term 335 days). Rates of O2 uptake by the gravid uterus, fetus and uteroplacental tissues were significant at both gestational ages and were 2- to 3-fold higher in late gestation than the mid-gestation values of 3338 ± 794, 1352 ± 258 and 2035 ± 602 µmol min-1, respectively (n = 4). Similarly, there were significant uptakes of glucose by the gravid uterus, fetus and uteroplacental tissues at both mid- and late gestation. However, unlike O2 uptake, glucose uptake by the uterus and uteroplacental tissues did not increase between mid- and late gestation. No significant uptakes or outputs of lactate were observed by the uterus or uteroplacental tissues at either gestational age, although there was a significant umbilical uptake of lactate in late but not mid-gestation. There was no change in the distribution of uterine O2 uptake between the fetus and uteroplacental tissues with increasing gestational age. The uteroplacental tissues accounted for about 50 % of the uterine O2 uptake at both gestational ages. In contrast, the proportion of the uterine glucose uptake used by the uteroplacental tissues decreased from 73.2 ± 2.1 % (n = 5) at mid-gestation to 61.1 ± 1.9 % (n = 4, P < 0.02) in late gestation. The gestational changes in uteroplacental carbohydrate metabolism in the mare differ from those seen in the ewe and may have important consequences for the duration and outcome of pregnancy in the mare. Experimental Physiology (2000) 85.5, 539-545.

In mammals that use the ventilatory system as the principal means of increasing heat loss, raising body temperature causes the adoption of a specialised breathing pattern known as panting and this is mediated by the thermoregulatory system in the preoptic area of the hypothalamus. In these species an additional respiratory drive is also present at raised body temperature, since breathing can reappear at low Pa,CO2 levels, when stimulation of chemoreceptors is minimal. It is not known whether the preoptic area is also the source of this additional drive. Rats do not pant but do possess this additional respiratory drive at raised body temperatures. We have therefore tested whether the preoptic area of the hypothalamus is the source of this additional respiratory drive in rats. Urethane anaesthesia and hyperoxia were used in eleven rats to minimise behavioural and chemical drives to breathe. The presence of the additional respiratory drive was indicated if rhythmic diaphragmatic EMG activity reappeared during hypocapnia (a mean Pa,CO2 level of 21 ± 2 mmHg, n = 11), induced by mechanical ventilation. The additional respiratory drive was absent at normal body temperature (37°C). When the temperature of the whole body was raised using an external source of radiant heat, the additional respiratory drive appeared at 40.6 ± 0.5°C (n = 3). In two further rats this drive was induced at normal body temperature by localised warming in the preoptic area of the intact hypothalamus. The additional respiratory drive appeared at similar temperatures to those in control rats in three rats following isolation of the hypothalamus from more rostral areas of the brain. In contrast, the additional respiratory drive failed to appear at these temperatures in three rats after isolating the hypothalamus from the caudal brainstem, by sectioning pathways medial to the medial forebrain bundle. Since the preoptic area is known to contain thermoreceptors and to receive afferents from peripheral thermoreceptors, the results show that this area is also the source of the additional respiratory drive at raised body temperature in anaesthetised rats. Experimental Physiology (2000) 85.5, 527-537.

G-protein coupled receptors (GPCRs) are key to maintaining uterine quiescence and inducing phasic contractions at term. However, the biochemical mechanisms whereby uterine GPCRs are desensitised and re-sensitised during these physiological conditions are unknown. For example, the number of oxytocin receptors (OTRs) on uterine myocytes decrease significantly after the addition of oxytocin. Therefore, further understanding of the desensitisation/re-sensitisation of the OTR and other uterine GPCRs during pregnancy may provide a target for more efficient tocolytic drugs and more selective ways to modulate uterine activity. Here, we briefly review some of the mechanisms that may be involved during OTR and other GPCR desensitisation. Experimental Physiology (2001) 86.2, 303-312.

This study examined post-exercise changes in corticospinal excitability in five 'elite' rowers and six non-rowers. Transcranial magnetic stimulation (TMS) was delivered to the motor cortex and bilateral electromyographic (EMG) recordings were made from erector spinae (ES) muscles at L3/L4 spinal level and from the first dorsal interosseous (FDI) muscle of the dominant hand. Each subject completed two exercise protocols on a rowing ergometer: a light exercise protocol at a sub-maximal output for 10 min and an intense exercise protocol at maximum output for 1 min. A trial of ten magnetic stimuli was delivered before each of the protocols and, on finishing exercise, further trials of ten stimuli were delivered every 2 min for a 16 min period. Amplitudes of motor-evoked potentials (MEPs) in each of the three test muscles were measured before exercise and during the recovery period after exercise. The non-rowers showed a brief facilitation of MEPs in ES 2 min after light and intense exercise that was only present in the elite rowers after intense exercise. In the period 4-16 min after light exercise, the mean (± S.E.M.) MEP amplitude (relative to pre-exercise levels) was less depressed in the elite rowers (79.4 ± 2.1 %) than in the non-rowers (60.9 ± 2.5 %) in the left ES but not significantly so in the right ES. MEP amplitudes in FDI were significantly larger in the elite rowers, averaging 119.0 ± 3.1 % pre-exercise levels, compared with 101.2 ± 5.8 % in the non-rowers. Pre-exercise MEP latencies were no different in the two groups. After light exercise MEP latencies became longer in the elite rowers (left ES, 16.1 ± 0.5 ms; right ES, 16.1 ± 0.4 ms; dominant FDI, 23.4 ± 0.2 ms) than in the non-rowers (left ES, 15.0 ± 0.3 ms; right ES, 15.2 ± 0.3 ms; dominant FDI, 21.5 ± 0.2 ms). There were no differences in MEP depression or latency between elite rowers and non-rowers after intense exercise. We conclude that the smaller degree of MEP depression in the elite rowers after light exercise reflects less central fatigue within corticospinal control pathways than that seen in the non-rowers. The longer latency of MEPs seen in the elite rowers may reflect recruitment of more slower-conducting fatigue-resistant motor units compared with the non-rowers. These differences may be because the energy requirements for the non-rowers during light exercise are closer to their maximum capacity, leading to more fatigue. This notion is supported by the lack of any difference between groups following intense exercise when both groups were working at their own maximum. Experimental Physiology (2002) 87.5, 593-600.

Lower body negative pressure (LBNP) reduces central venous pressure (CVP) and cardiac output. The elderly are reported to have a limited capacity to increase cardiac output by increasing heart rate (HR), are especially dependent on end diastolic volume to maintain stroke volume and therefore should be especially vulnerable to LBNP. The present study compared the effects of LBNP in the young and old. Stroke volume was assessed non-invasively as stroke distance (SD) by aortovelography. Two groups of healthy male volunteers were studied: eight young (29.7 ± 2.0 years, mean ± S.E.M.) and nine old (70.1 ± 0.9 years). LBNP was applied progressively at 17.5, 35 and 50 mmHg in 20 min steps, with measurements taken during each steady state. There were similar, significant, falls in CVP in both groups. SD fell significantly in both groups from respective control values of 24.8 ± 1.6 and 16.6 ± 0.9 cm to 12.5 ± 1.3 and 8.9 ± 0.4 cm at a LBNP of 50 mmHg. Although SD in the elderly was significantly lower than in the young, the LBNP-induced changes were not different between groups. Both groups produced similar significant increases in vascular resistance, HR, plasma vasopressin (AVP) and noradrenaline. Mean arterial blood pressure (MBP) and plasma adrenaline did not change significantly. Therefore healthy old men respond to LBNP in a similar manner to the young, although MBP and SD are regulated around different baselines in the two groups. Experimental Physiology (2001) 86.3, 427-435.

The neuroendocrine response to surgical trauma is a complex set of hormonal and metabolic changes evoked by anxiety, blood loss, tissue damage, visceral handling, and also by the anaesthetic drugs and procedures (Traynor & Hall, 1981). A useful approach to understanding the surgery-induced stress syndrome is to individualize these stressful stimuli in order to explore the specific effects of anxiety, anaesthesia or surgery itself on the endocrine and metabolic responses that are observed altogether. The relative importance of each element contributing to surgical stress should be better characterized in order to provide the rationale for improving the management of surgical patients. For instance, it remains unclear whether the physiological alterations induced by surgical stress are a single syndrome arising from the addition of several stressors or comprise parallel responses to each stressor, with some convergent end-points.