Feto-maternal vascular (PDF-M) and amniotic-maternal (PDA-M) potential differences were measured simultaneously on seven occasions in six conscious pigs of 100-106 days gestation. Resting values of PDF-M and PDA-M were not significantly different although the range was wide. Fetal intravascular injection of 20 µg adrenaline, but not of saline, was associated with a prompt reversible change, of equal magnitude, in both PDF-M and PDA-M. In some experiments polarity was reversed. Feto-amniotic potential difference did not change. There was no change in fetal plasma K+ and Na+ concentrations. Because of the simultaneous and equal alterations in PDF-M and PDA-M following adrenaline and the anatomical configuration of the pig conceptus, we conclude that the catecholamine modifiable component of PDF-M is generated by electrogenesis in the pig placenta, probably by its chorionic (trophoblastic) cell layer.

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).

We have previously shown that feeding 50 ml of colostrum can increase the thermogenic activity of brown adipose tissue (BAT) in newborn lambs maintained at a warm (30¡C) ambient temperature. This study further examines the effect of ambient temperature on BAT and thermoregulation by investigating the response to feeding 50 ml of water. Immediately after vaginal birth, lambs were placed in either a warm (30¡C) or cool (15¡C) environment at ambient temperature and measurements of colonic temperature and heat production were recorded for 6 h. Lambs were fed 50 ml of water when 5 h old. The level of guanosine 5'-diphosphate (GDP) binding was higher, but adrenaline content lower in BAT sampled from lambs maintained at 15¡C compared with those at 30¡C. Feeding was associated with an increase in colonic temperature and plasma concentrations of glucose and non-esterified fatty acids in lambs maintained at 15¡C only. In this group plasma concentrations of adrenaline and dopamine declined after feeding, but noradrenaline concentrations were not influenced by feeding in either group of lambs. O2 consumption and CO2 production were higher in lambs maintained at 15¡C but were not influenced by ambient temperature or feeding. It is concluded that feeding a small volume of water can influence thermoregulation by a mechanism that is dependent on the ambient temperature at which the lamb is maintained.

The shortcomings of diffusion as a mechanism of glucose transfer across cell membranes date back to the last century. The early work, mostly qualitative, was greatly extended by LeFevre in America and by Wilbrandt in Switzerland, who reported their quantitative studies at the Bangor Symposium of The Society of Experimental Biology in 1953 (LeFevre, 1954; Wilbrandt, 1954). Widdas (1952) published simple carrier kinetics for glucose transfer which predicted the phenomenon of uphill transfer by counterflow. However, in that 1952 paper it was carefully pointed out that a good fit to the kinetics did not define the details of the mechanism. Nevertheless, the reverse is true: namely, any viable scheme of working must be consistent with the established kinetic properties. For instance the kinetics of uphill transfer by counterflow (confirmed four years later by Park, Post, Kalman, Wright, Johnson & Morgan, 1956; Rosenherg & Wilbrandt, 1957) clearly exclude a simple water channel through the membrane.The concept of a mobile membrane carrier on which the early kinetics were based was variously modified to meet newer developments, which included asymmetric affinities on the outside and inside of the red cell membrane. The mobile carrier has now been superseded by the concept of membrane protein transporters. Nevertheless, some of the nomenculture, such as carrier transport and carrier catalysis (Krämer, 1994), has persisted although it no longer conveys all the subtleties of the transfer mechanism.

In patients following myocardial infarction (MI), exercise tolerance and muscular strength are often markedly reduced. The purpose of this investigation was to determine if calcium (Ca2+) uptake and release by skeletal muscle sarcoplasmic reticulum (SR) are altered following MI and if such changes are associated with diminished muscular performance. SR vesicles were isolated from rat gastrocnemius muscle at 6 and 12 weeks following MI (via left coronary artery ligation) or sham surgery. At both post-surgery intervals, the rates of Ca2+ uptake (measured using fura-2) were 35 % greater in the MI group. In addition, the rates of Ca2+ release were increased in the MI group by 10 and 30 % at 6 and 12 weeks, respectively. At 12 weeks post-surgery, animals of the MI group showed significant reductions in in situ twitch and tetanic forces and significant elevations in the rates of tension increase and decrease. These data indicate that SR Ca2+ exchange is altered following MI. In addition, changes in SR function are associated with changes in force production by the whole muscle.

Four adult Corriedale sheep were used in an experiment divided into three parts. In part 1 a primed continuous infusion of [6,6-2H2]glucose was infused for 7 h. The first 3 h was the control period, from 3 to 7 h glucose-dependent insulinotropic polypeptide (GIP) was infused, and from 5 to 7 h somatostatin was infused. Part 2 of the experiment was the same as for part 1 except that insulin was infused between 3 h and 7 h and GIP was infused between 5 and 7 h. Coincident with the insulin infusion, normal glucose was also infused at a variable rate in order to keep the plasma glucose at basal levels. In part 3 of the experiment [6,6-2H2]glucose was infused for 5 h and somatostatin was infused between 3 and 5 h. Measurements of glucose turnover were made in the last 40 min of the control, GIP only, insulin only, somatostatin only, GIP plus somatostatin and GIP plus insulin infusion periods. Plasma insulin levels were reduced to the limit of detection by the somatostatin infusion; under such conditions whole-body glucose uptake should be entirely non-insulin-mediated (NIMGU). Expressing glucose disposal as glucose metabolic clearance rate demonstrated that elevated, but still physiological GIP levels had no effect on NIMGU but significantly increased insulin-mediated glucose uptake when plasma insulin levels were similar to levels typically observed after a meal. These results indicate that in sheep, GIP may enhance insulin action with respect to glucose disposal following a meal, but has no effect on glucose disposal pathways not responsive to insulin.

The abdominal circulation contains a high proportion of the total blood volume and this can change either passively in response to changes in vascular distending pressure or actively (termed a capacitance response) to changes in sympathetic nervous activity. The liver is the largest abdominal organ and this study was designed to evaluate its potential contribution to overall vascular capacitance and compliance. In chloralose anaesthetized dogs, the liver was vascularly isolated, perfused through the portal vein and hepatic artery at either constant pressures or constant flows and drained from the hepatic veins at constant pressure. Changes in vascular resistance were assessed from changes in inflow pressures or flows and hepatic blood volume was determined by differences between net inflow and outflow. During constant flow perfusion the change in hepatic volume (capacitance change) in response to supramaximal stimulation of sympathetic nerves at 16 Hz was (mean ± S.E.M.) -2·40 ± 0·61 ml (kg body weight)-1. This response was not significantly different during constant pressure perfusion. The changes in portal venous and hepatic arterial pressures during stimulation at constant flow perfusion were +0·67 ± 0·13 and +4·92 ± 0·67 kPa, respectively. The compliance of the liver, assessed as the change in volume to a change in hepatic venous pressure, was +5·44 ± 0·18 ml kg-1 kPa-1. These results indicate that the liver has a major capacitance role, comparable to that of the canine spleen and, in addition, is highly compliant. No evidence was found to suggest that a sphincter on the hepatic outflow exists. Assuming similar responses occur in humans, who do not possess a large contractile spleen, the liver would be the most important controllable blood reservoir in the body.

Net sugar import by human erythrocytes consists of ATP-modulated rapid and slow phases while sugar export consists of a single slow phase. We have proposed that this behaviour results from obligate substrate tunnelling from transporter to bulk cytosol through a complex containing high-affinity, low-capacity sugar binding sites (Cloherty, Sultzman, Zottola & Carruthers, 1995). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is known to compartmentalize ATP delivery to erythrocyte membrane ATPases and interact directly with the erythrocyte glucose transporter in vitro. The present study examines the possibility that GAPDH is an obligate component of the hypothesized sugar-binding complex. GAPDH remains associated with the erythrocyte membrane following cell lysis and remains associated with the cytoskeleton under conditions where more than 99 % of the membrane glucose transport protein (GLUT1) is released by detergent (Triton X-100). GAPDH is released from erythrocyte membranes upon exposure to Mg.ATP or to NADH. ATP displacement of membrane-bound GAPDH is half-maximal at 200 µM ATP and appears to involve ATP interaction with multiple, co-operative sites. GAPDH interaction with purified tetrameric GLUT1 is saturable, co-operative and also inhibited by ATP. ATP inhibition of GAPDH binding to purified tetrameric GLUT1 is less effective than ATP inhibition of GAPDH binding to intact erythrocyte membranes. Removal of cellular GAPDH by exposing erythrocyte membranes to NADH prior to membrane resealing neither affects ATP modulation of sugar transport nor reduces biphasic net sugar uptake to a single phase. We conclude that ATP-sensitive GAPDH interaction with the cytoplasmic surface of erythrocyte membranes and GLUT1 is responsible neither for ATP modulation of sugar transport nor for multiphasic net sugar import by human red cells.

The effects of cyclical, passive manipulation (PM, 30 min day-1, 5 days week-1 for 6 months) mimicking the length excursions observed during stepping on the mechanical and associated biochemical properties of the inactive cat soleus muscle were determined in five cats. Inactivity was produced via spinal cord isolation (SI), i.e. complete spinal cord transections at low thoracic and high sacral levels and bilateral dorsal rhizotomy between the transection sites. Passive manipulation was administered to one leg of each SI cat. Compared with normal controls, SI resulted in [similar]70 % decrease in weight, an 80 % decrease in maximum tetanic tension (Po) and an [similar]100 % increase in maximum rate of shortening (Vmax) and myosin adenosine triphosphatase (mATPase) activity of the soleus. The passive manipulation regime partially ameliorated these effects. When compared with the control SI soleus, the SI-PM soleus weight and maximum tetanic tension were 12 and 21 % higher, respectively, and the Vmax and mATPase activity 21 and 12 % (p > 0·05) lower, respectively. Thus, inactivity resulted in a smaller and faster muscle, whereas passive manipulation for only 30 min a day tended to maintain these properties closer to normal control values. The results suggest a potential therapeutic effect of short bouts of cyclical, passive manipulation on otherwise inactive skeletal muscles.

Investigations of intestinal secretion are often performed under anaesthesia. This study evaluates the influence of anaesthetic agents on the intestinal secretion induced by cholera toxin (CT) in the pig. CT was instilled for 4 h in ligated jejunal loops under anaesthesia with halothane, saffan, [alpha]-chloralose, or propofol. Cardiovascular parameters, blood gas data, plasma cortisol levels, net fluid accumulation, intraluminal mediators (serotonin (5-HT), prostaglandin E2 (PGE2)) and electrolyte concentrations in the accumulated fluid were determined. The systolic blood pressure and heart rate was highest for saffan-anaesthetized pigs (blood pressure: saffan > [alpha]-chloralose > propofol = halothane; heart rate: saffan > [alpha]-chloralose = propofol = halothane), while blood gases and cortisol levels were within the same range. CT induced a dose-dependent fluid accumulation under all four anaesthetics. The fluid accumulation was significantly higher in pigs treated with saffan, [alpha]-chloralose and propofol than in halothane-treated pigs (saffan = [alpha]-chloralose > propofol > halothane). There was no significant difference in electrolyte concentrations in the accumulated fluid or in the luminal content of 5-HT and PGE2 between anaesthetics. The results demonstrate that anaesthetic agents profoundly influence the secretory response in the small intestine and indicate the importance of the choice of anaesthetic in this type of experiment.

Newborn pigs rely essentially on shivering thermogenesis in the cold. In order to understand the rapid postnatal enhancement of thermogenic capacities in piglets, the oxygen and nutrient uptake of hindquarters was measured in vivo in 1- (n = 6) and 5-day-old (n = 6) animals at thermal neutrality and during cold exposure. The hindquarters were considered to represent a skeletal muscle compartment. Indirect calorimetry and arterio-venous techniques were used. The cold challenge (23¡C at 1 day old and 15¡C at 5 days old for 90 min) induced a similar increase (+90 %) in regulatory heat production at both ages. Hindquarters blood flow was higher at 5 days than 1 day old at thermal neutrality (26 ± 3 vs. 17 ± 1 ml min-1 (100 g hindquarters)-1) and its increase in the cold was much more marked (+65 % at 5 days old vs. +25 % at 1 day old). Oxygen extraction by the hindquarters rose from 30-35 % at thermal neutrality to 65-70 % in the cold at both ages. The calculated contribution of skeletal muscle to total oxygen consumption averaged 34-40 % at thermal neutrality and 50-64 % in the cold and skeletal muscle was the major contributor to regulatory thermogenesis. Based on hindquarters glucose uptake and lactate release, carbohydrate appeared to be an important fuel for shivering. However, net uptake of fatty acids increased progressively during cold exposure at 5 days old. The enhancement in muscular blood supply and fatty acid utilization during shivering is probably related to the postnatal improvement in the thermoregulatory response of the piglet.

Growing pigs were fed diets supplying 45 % (low), 70 % (intermediate) and 100 % (high) recommended dietary allowances of calcium (the Ca:P ratio was kept constant), but otherwise adequate in nutrients. The effects of varying calcium and phosphorus intakes on bone and plasma osteocalcin were monitored. Mineral content of the diet did not affect feed conversion and live weight gain. Plasma phosphorus concentrations decreased significantly in pigs fed a low mineral diet compared with those fed the high mineral diet, but there were no changes in plasma calcium and osteocalcin concentrations. Bones from the low mineral group had marked reductions in dry matter, calcium and phosphorus contents, as well as increased collagen, pyridinoline and deoxypyridinoline concentrations: osteocalcin concentrations in bone were unaffected by treatment. The results showed no direct link between osteocalcin and the degree of bone mineralization.

The purpose of this study was to quantify the possible reduction in ventilation that could be attributed to changes in cerebral blood flow (CBF) with hypoxia to determine whether it could be of sufficient magnitude to underlie hypoxic ventilatory decline (HVD). Six subjects underwent 20 min of isocapnic hypoxia (end-tidal PO2, 50 mmHg). An index of CBF was obtained using transcranial Doppler ultrasound of the middle cerebral artery. The CBF sensitivities to hypoxia and hypercapnia were obtained from the percentage changes in CBF between the last 3 min of the hypoxic or hypercapnic exposure and the 3 min period prior to the exposure. The magnitude of HVD during hypoxia was estimated by fitting a simple model of the ventilatory response to the hypoxic stimulus. The predicted fall in expiratory ventilation ([Vdot]E) due to a reduction in brain PCO2 generated by the increase in CBF with hypoxia in all subjects was less than the measured magnitude of HVD (33 %). Thus, the results from this study suggest that, in awake humans, changes in CBF during acute isocapnic hypoxia are quantitatively insufficient to underlie HVD in humans.

The effects of exogenous arginine vasotocin (AVT), isotocin (IT) and melatonin on the blood pressure of conscious Atlantic cod (Gadus morhua) were examined. Ventral aortic blood pressure (PVA) was recorded from a cannula inserted into the afferent branchial artery of the third gill arch. Dorsal aortic blood pressure (PDA) was recorded via a cannula implanted into the efferent branchial artery in the same gill arch. Each fish received two doses (10 and 50 ng kg-1) of AVT, IT and melatonin. AVT was also administered in combination with melatonin. Injection of 10 ng kg-1 AVT produced significant hypertension, especially in animals injected during the daytime. In contrast, the same dose of IT induced no significant change in either PVA or PDA. Administration of 10 ng kg-1 melatonin at night caused a long-lasting decrease in both parameters. Melatonin also inhibited the increase in blood pressure elicited by AVT. These results indicate that AVT, but not IT, is vasopressor in the cod. The effects of combined administration of melatonin and AVT show the antihypertensive action of melatonin in AVT-induced hypertension.

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.

The inward transport of two purines, adenosine and hypoxanthine, at 37¡C by horse erythrocytes was compared. No mediated transport of adenosine was detected in horse erythrocytes, nor was saturable, high-affinity binding of the potent facilitated-diffusion inhibitor nitrobenzylthioinosine demonstrable in horse erythrocyte membranes. In contrast, erythrocytes from most horses possessed a saturable sodium-dependent hypoxanthine transporter (apparent Km, 100 ± 28 µM; Vmax, 0·20 ± 0·08 mmol (l cells)-1 h-1; means ± S.E.M., n = 5). Guanine inhibited hypoxanthine influx (apparent Ki, 24 ± 6 µM), but adenine and xanthine had no effect. Unlike human erythrocytes, no sodium-independent hypoxanthine transporter was detected in horse erythrocytes. There are, however, a small number of animals ([similar]15 %) whose erythrocytes fail to transport hypoxanthine. This variation appears to be under genetic control, but the precise nature of the control is unknown.

To characterize an 'electrocholecystogram' (EChG) for the normal gall bladder (GB) that might act as a standard for the evaluation of pathological electrocholecystograms of the diseased GB, ten mongrel dogs (14·4 ± 3·2 kg) were studied. Under anaesthesia, the abdomen was opened and three silver-silver chloride electrodes were sutured to the GB serosa. The GB pressure was measured by a perfused catheter introduced through the fundus. The response of the myoelectrical activity of the GB to balloon distension was tested and the direction of electrical waves was defined by GB myotomies. Pacesetter potentials (PPs) were recorded exhibiting the same frequency, amplitude and velocity of conduction from the three electrodes of each dog on all test days. Action potentials (APs) followed the PPs randomly and were associated with a rise of the GB pressure. Balloon distension of the GB caused increased PP and AP frequency. The electrical waves showed proximally but not distally to GB myotomy, indicating that they propagate proximo-distally towards the cystic duct. To conclude, the GB possesses electrical waves which are probably initiated from a 'pacemaker' at the GB fundus. A normal EChG could be characterized in the canine model. It is suggested that this EChG might show changes in gall bladder diseases and might thus act as an investigative tool, provided it can be developed to be performed percutaneously.

Exposure to a temperature of 14¡C was used to induce a progressive hypothermia in fourteen conscious newborn piglets. Heat production, body (rectal) and skin (between the shoulders) temperatures and shivering intensity assessed as the electromyographic activity (EMG) of longissimus thoracis muscle were measured until body temperature reached 30¡C and during a recovery period of 2 h at an ambient temperature of 24¡C (n = 7) or 34¡C (n = 7). During body cooling, heat production increased up to 9·67 ± 1·28 W (kg BW)-1, but started to decrease below a body temperature threshold of 34·4 ± 0·7¡C. EMG activity increased (P < 0·023) curvilinearly during body cooling; the main increase occurred between body temperatures of 38 and 33¡C (+142 %, P < 0·001), and changes in EMG activity between 33 and 30¡C were not significant (+18 %, P > 0·1). A marked increase in circulating levels of glucose (+312 %, P < 0·001), glucagon (+76 %, P < 0·05), adrenaline (+172 %, P < 0·05) and noradrenaline (+113 %, P < 0·05) occurred during body cooling. Insulin levels were not detectable at 2 h of life and increased during body cooling. During 2 h of rewarming at 24¡C, heat production and EMG activity remained elevated, changes in carbohydrate metabolism were not completely reversed and the final body temperature was only 35·6 ± 0·9¡C. Rewarming of the piglets was faster at 34¡C. There was a net influx of heat into the animals and heat production and shivering activity decreased when body temperature reached 33·9 ± 0·5¡C; the final body temperature was 37·5 ± 0·2¡C. Circulating levels of lactate, glucagon and catecholamines returned to control levels. These results show that in conscious piglets exposed to a constant cold temperature there is an inverse relationship between EMG activity and body temperature during moderate hypothermia and that the thermoregulatory response and carbohydrate metabolism of the piglet are seriously impaired below a body temperature of 34¡C.

Parotid secretion has been investigated in anaesthetized lambs in the presence and absence of N[omega]- nitro-L-arginine methyl ester (L-NAME) and sodium nitroprusside to block de novo synthesis of nitric oxide (NO). Following administration of L-NAME the basal rate of flow was unaffected and changes in electrolyte secretion failed to achieve statistical significance but there was a significant fall in the basal rate of protein secretion. The flow of parotid saliva which occurred in response to stimulation of the parasympathetic innervation was reduced by 34 % and sodium output was reduced in approximately the same proportion. L-NAME had no significant effect on these parameters during stimulation of the sympathetic innervation. During combined stimulation of the parasympathetic and sympathetic innervations L-NAME caused a reduction in parotid salivary flow and sodium output which was roughly the same as that observed during parasympathetic stimulation alone. However, L-NAME caused a much greater reduction in protein output during each of these experimental protocols: -92 % during parasympathetic stimulation, -63 % during sympathetic stimulation, and -60 % during combined stimulation. Whereas the absolute amount of protein secreted was reduced after L-NAME in each instance, the extent of potentiation of protein output recorded during combined stimulation was increased roughly fivefold. It is concluded that the output of protein in response to autonomic stimulation exhibits a greater NO dependence than either the flow of saliva or secretion of electrolytes in this gland.