An investigation was undertaken into the potential role of nitric oxide (NO) and its interaction with renal sympathetic nerves in mediating renal responses to acute saline volume expansion (VE). Groups of anaesthetized Wistar rats with innervated and denervated kidneys were subjected to VE, 0·25 % body wt min-1 for 40 min, in the presence and absence of nitric oxide synthase (NOS) inhibitors, NG-nitro-{fontsize L-arginine-methyl-ester ({fontsize L-NAME, non-selective), aminoguanidine (AG, relatively selective for inducible NOS (iNOS)), and 7-nitroindazole (7-NI, relatively selective for neuronal NOS (nNOS)). Pretreatment with {fontsize L-NAME or AG enhanced the cumulative sodium excretion (CuUNaV) after 40 min VE in the innervated kidneys by 27 and 23 % (both P < 0·001), respectively, compared to the untreated control group, whereas they were without effect in the denervated kidneys. Cumulative urine flow (CuUV) after VE in {fontsize L-NAME- and AG-treated groups was enhanced in both kidneys, by some 17-21 % in the denervated (P < 0·01) and 37-39 % in the innervated kidneys (P < 0·001) by comparison with the corresponding untreated controls. 7-NI had no effect on CuUV, but reduced CuUNaV in the denervated kidneys by 25 % (P < 0·01) when compared to the control group. The results suggested that NO, possibly generated by endothelial NOS (eNOS) and iNOS, was a contributory factor in mediating the renal response to VE. There appeared to be a tonic inhibitory action of NO on water excretion which was renal nerve independent, whereas its impact on sodium handling appeared to be dependent upon a background level of renal nerve activity. Experimental Physiology (2001) 86.1, 47-54.

The regulation of vascular tone includes modulation of contractile element calcium sensitivity. We tested the involvement of the Rho-associated protein kinase p160ROCK in tone and calcium sensitivity of cannulated rat mesenteric small arteries. These vessels developed basal tone and showed myogenic responses upon pressure steps, resulting from an increase in calcium in combination with a high contractile element calcium sensitivity. Y-27632, believed to be a specific p160ROCK inhibitor, caused concentration-dependent inhibition of basal tone, with near full inhibition at 3 µM. At this concentration, myogenic responses were absent and stepwise pressure elevation resulted in severe vascular distension. Y-27632 did not affect pressure-induced changes in intracellular calcium but rather reduced pressure-induced as well as phenylephrine-induced calcium sensitisation. Thus in the presence of the blocker, for a given calcium concentration, tone was greatly reduced, and the divergence in sensitivity between pressure and phenylephrine as stimuli on the one hand and potassium on the other disappeared. K+ (125 mM) and ionomycin still caused contraction in the presence of the p160ROCK blocker. These data show that in pressurised small arteries the Rho-p160ROCK pathway is active in the absence of vasoconstrictors, keeping the vessels in a state of high calcium sensitivity and basal tone. Experimental Physiology (2001) 86.5, 585-592.

Stimulation of left ventricular mechanoreceptors was believed not only to exert important effects on the circulation, but also to influence the responses to baroreceptor reflexes. However, most previous work is flawed due to inadequate localisation of stimuli to specific reflexogenic areas. In this study, we applied a discrete stimulus to left ventricular mechanoreceptors to examine other reflexes known to effect the circulation. Dogs were anaesthetised, artificially ventilated and a cardiopulmonary bypass established. The pressure distending the left ventricle was controlled through an apical cannula with the aortic valve obstructed by a balloon. Changes in ventricular systolic and end-diastolic pressure had only a small effect on vascular resistance, assessed as perfusion pressure in the systemic circulation (flow constant). Responses to changes in carotid or coronary pressure or to stimulation of chemosensitive afferents by injecting veratridine into the coronary circulation were always much larger. Responses to stimulation of these reflexes were little affected by the level of stimulus to the ventricular receptors. These experiments confirm that responses to stimulation of ventricular mechanoreceptors are very small and show that they remain small at different levels of input to other baroreceptive regions. There was no evidence of interaction between ventricular mechanoreceptor reflexes and carotid or coronary baroreceptors or ventricular chemosensitive reflexes. Experimental Physiology (2001) 86.3, 381-390.

Increased fetal lung expansion, induced by tracheal obstruction (TO), is a potent stimulus for fetal lung growth, but rapidly reduces surfactant protein (SP) mRNA levels. Our aim was to determine the time course for the re-expression of the surfactant proteins in fetal lung tissue following the release of a TO and to relate these to the changes in lung liquid volume. Fetal sheep were exposed to either: (1) no treatment (controls); (2) 4 days of TO; (3) 4 days of TO, followed by release of the obstruction for 24 h; (4) 4 days of TO followed by release of the obstruction for 3 days. Four days of TO increased lung liquid volumes from 26.8 ± 1.9 to 72.0 ± 5.6 ml kg-1 and reduced SP-A, SP-B and SP-C mRNA levels to 38.5 ± 10.7, 56.8 ± 10.3 and 18.3 ± 5.3 % of control values, respectively. One day after TO release, lung liquid volumes were reduced to 17.4 ± 5.3 ml kg-1 (control 128 days, 31.0 ± 3.8 ml kg-1) and SP-A and SP-B mRNA levels were not different from control levels. In contrast, SP-C mRNA levels only increased to 45.4 ± 17.3 % of control. Three days after TO release, lung liquid volumes increased to 48.0 ± 8.5 ml kg-1 and SP-A and SP-B mRNA levels were reduced to 48.8 ± 10.2 % and 71.5 ± 19.8 % of control, respectively; SP-C mRNA levels remained at 35.3 ± 12.3 % of control. Following the release of a TO, SP-A, SP-B and SP-C mRNA levels were closely and inversely related to the volume of lung liquid. Based on these relationships, the lung liquid volumes that equate to 100 % expression were considerably less than control lung volumes (< 10 vs. 30-40 ml kg-1) in fetuses of this age. Thus, the changes in fetal lung SP-A, SP-B and SP-C mRNA levels following the release of a TO are variable, differ between the proteins and are closely related to the changes in lung liquid volumes. We conclude that the re-expression of surfactant proteins following TO is variable and that the change in lung liquid volume is potentially a good indicator for surfactant protein re-expression. Experimental Physiology (2001) 86.1, 55-63.

Maternal and fetal body temperatures were measured in five Boer goats, of mean mass 64 ± 8 kg, using temperature-sensitive radiotelemeters implanted intra-abdominally. Body temperatures were recorded every 5 min. Throughout the last month of gestation, fetal temperature was approximately 0.6 oC higher than that of the mother, in normal laboratory conditions (ambient air temperature: 21-24 oC). This feto-maternal temperature difference between the goat fetus and its mother is similar to that found in other mammals, including sheep. When the pregnant goats were subjected to short-term heating and cooling, the difference between maternal and fetal body temperatures changed. Thus the mean difference between fetal and maternal body temperatures decreased from 0.4 to 0.2 oC during 2 h of heating, while it widened from 0.3 to 0.7 oC during 6 h of cooling. These data support the idea that the fetus is thermally protected from excursions of body temperature during changes in the mother's thermal environment. Reports of goat stock losses and abortions during cold spells in their natural habitats may be the result of more severe and/or prolonged cold exposures that not only adversely affect fetal or maternal body temperature, but also influence other aspects of metabolism. Experimental Physiology (2001) 86.2, 199-204.

To determine the functional role of nitric oxide (NO) in regulating vascular conductance during high intensity dynamic exercise in skeletal muscles composed of all major fibre types, female Wistar rats (277 ± 4 g; n = 7) were run on a motor-driven treadmill at a speed and gradient (60 m min-1, 10 % gradient) established to yield maximal oxygen uptake (V˙O2,max). Vascular conductance (ml min-1 (100 g)-1 mmHg-1), defined as blood flow normalised to mean arterial pressure (MAP), was determined using radiolabelled microspheres during exercise before and after NO synthase (NOS) inhibition with N G-nitro-L-arginine methyl ester (L-NAME; 10 mg kg-1, I.A.). The administration of L-NAME increased MAP from pre-L-NAME baseline values, demonstrating that NOS activity is reduced. The administration of L-NAME also reduced vascular conductance in 20 of the 28 individual hindlimb muscles or muscle parts examined during high speed treadmill exercise. These reductions in vascular conductance correlated linearly with the estimated sum of the percentage of slow twitch oxidative (SO) and fast twitch oxidative glycolytic (FOG) types of fibres in each muscle (Δconductance = -0.0082(%SO + %FOG) - 0.0105; r = 0.66; P < 0.001). However, if the reduction in vascular conductance found in the individual hindquarter muscles or muscle parts was expressed as a percentage decrease from the pre-L-NAME value (%Δ = (pre-L-NAME conductance - post-L-NAME conductance)/ pre-L-NAME conductance × 100), then the reduction in vascular conductance was similar in all muscles examined (average %Δ = -23 ± 2 %). These results suggest that NO contributes substantially to the regulation of vascular conductance within and among muscles of the rat hindquarter during high intensity exercise. When expressed in absolute terms, the results suggest that the contribution of NO to the regulation of vascular conductance during high intensity exercise is greater in muscles that possess a high oxidative capacity. In contrast, if results are expressed in relative terms, then the contribution of NO to the regulation of vascular conductance during high intensity exercise is similar across the different locomotor muscles located in the rat hindlimb and independent of the fibre type composition. Experimental Physiology (2001) 86.6, 749-757.

Interstitial adenosine concentrations in red soleus (SL) or white extensor digitorum longus (EDL) muscles of anaesthetised rats were determined using microdialysis and HPLC. Systemic hypoxia was induced by ventilating the animals with 10 % oxygen in nitrogen for 15 min: arterial PO2 decreased from 111.8 ± 10.9 to 42.2 ± 4.3 mmHg (n = 4; P < 0.01) and mean systemic arterial blood pressure from 97.6 ± 4.9 to 59.0 ± 3.6 mmHg (n = 22; P < 0.001). The interstitial adenosine concentration was not significantly changed from its control values of 294 ± 44 nM (n = 20) in EDL and 302 ± 36 nM (n = 20) in SL during hypoxia or the recovery period. The interstitial lactate concentration did not change in the early part of the hypoxia but increased from 1.0 ± 0.2 to 1.4 ± 0.3 mM (n = 6; P < 0.05) in SL and from 2.0 ± 0.4 to 2.4 ± 0.4 mM (n = 6; P < 0.05) in EDL during the later part of the hypoxia, and remained elevated in the recovery period. Muscle contractions (2 Hz for 15 min) produced a transient increase in the interstitial adenosine concentration of SL from 150 ± 35 to 244 ± 75 nM (n = 10; P < 0.05) during the first 5 min of stimulation. In EDL the interstitial adenosine concentration increased from 145 ± 50 to 435 ± 144 nM (n = 10; P < 0.05) in the later part of the contraction and remained elevated in the early part of the recovery period. These data suggest that: (i) in systemic hypoxia adenosine does not appear in the interstitial space, which rules out its release from skeletal muscle, although it may be formed by the vascular tissues in this condition; (ii) adenosine is formed in the interstitial space of skeletal muscle during muscle contractions; (iii) there is slow clearance of adenosine from the interstitial space of white muscle, perhaps due to the low vascularity of the tissue. Experimental Physiology (2001) 86.5, 593-598.

We determined the interaction of diet and training on metabolic adaptations in skeletal muscle and liver, and the consequences of these adaptations for endurance. Eighty rats performed a baseline treadmill run to exhaustion at 16 m min-1 (RUN1) and were then divided into two groups and given one of two diets: high carbohydrate (CHO) or high fat (FAT). Each dietary group was then divided into one of four subgroups: sedentary control that performed no training (NT); low-intensity running (8 m min-1; LOW) and two groups who trained at their maximal voluntary running speed without electrical stimulation (28 m min-1; VMAX). Training volume was identical for LOW and VMAX (1000 m session-1) and animals ran 4 days week-1 for 8 weeks. To assess the interaction of the higher intensity exercise with diet, a second endurance test (RUN2) was undertaken after 6 weeks at either 16 m min-1 or 28 m min-1. The NT group ran for a longer duration (increase of 77 %) after FAT than CHO (239 ± 28 vs. 135 ± 30 min, P < 0.05) at 16 m min-1. There were no differences in RUN2 for the LOW group when rats ran at 16 m min-1 (454 ± 86 vs. 427 ± 75 min for CHO and FAT groups, respectively), but rats in the VMAX group fed FAT ran longer than rats fed CHO at 28 m min-1 (100 ± 28 vs. 58 ± 11 min, respectively, P < 0.05). FAT increased the activities of the enzymes citrate synthase, β-hydroxyacyl-CoA dehydrogenase and carnitine palmitoyl-transferase compared to CHO (P < 0.01), but there was no systematic effect of training. We conclude: (1) there was no additive effect of a high-fat diet on endurance performance when rats performed low-intensity training; (2) running performance at 28 m min-1 was only enhanced by a high-fat diet after more intense training; (3) diet-induced and training-induced adaptations that increase exercise capacity may be under independent control. Experimental Physiology (2001) 86.4, 499-508.

Despite marked differences in both the extent of physical activity and in muscle metabolism and structure between tetraplegic and control subjects, the glycogen content in the skeletal muscle of both groups is similar. We determined whether this similarity could be explained by the activities of key enzymes of glycogen metabolism. Muscle biopsies were analysed for glycogen synthase (GS) and glycogen phosphorylase (GP) activities, as well as for metabolites. Glycogen content did not differ significantly between the two groups. Total glycogen synthase activity was reduced by almost 60 % in tetraplegics (P < 0.01), whereas total phosphorylase activity did not differ between groups. GS fractional activity did not differ between groups, whereas phosphorylase fractional activity (-/+ AMP) was significantly higher in the tetraplegics (0.08 ± 0.01, control; 0.25 ± 0.02, tetraplegics; P < 0.001). Neither uridine diphosphate (UDP)-glucose nor glucose 6-phosphate (G-6-P) content in muscle differed significantly between groups. These data demonstrate that, in tetraplegics, muscle glycogen content is preserved despite decreases in GS activity and increases in phosphorylase fractional activity. Muscle paralysis has differential effects on the activities of GS and GP. Experimental Physiology (2001) 86.2, 205-209.

In this study we tested the hypothesis that, compared to young adult rats, senescent rats have a reduced ability to respond to muscle unloading. Unloading of the muscles was induced by hindlimb suspension (HS) of young adult and senescent rats for 21 days. Plantaris muscles from young adult rats had significantly higher levels of myogenin mRNA and protein (890 % and 314 %, respectively, P < 0.05) than plantaris muscles from senescent rats and also a higher MyoD mRNA level (280 %, P < 0.05), but ageing did not increase MyoD protein levels. Although HS did not increase plantaris mRNA or protein levels of myogenin or MyoD in senescent rats (P = 0.22), myogenin mRNA and protein levels increased by 850 % and 580 % respectively, and MyoD mRNA and protein levels by 235 % and 1600 %, respectively in young adult rats (P < 0.05). Soleus muscles from senescent rats had 150 % and 85 % greater myogenin and MyoD mRNA levels, respectively (P < 0.05), than soleus muscles from young adult rats, whereas protein levels of myogenin were similar (P > 0.05) and MyoD protein levels were 60 % lower in the muscle of senescent rats (P < 0.05). In young rats, soleus muscle mRNA levels of myogenin and MyoD were not altered by HS but myogenin protein levels decreased by 57 % (P < 0.05) whereas MyoD protein levels increased by 187 % (P < 0.05). In senescent rats, HS decreased soleus muscle myogenin mRNA and protein levels by 42 % and 26 % respectively (P < 0.05), but MyoD protein and mRNA levels were not changed. MRF4 levels were not affected by ageing in either muscle. These data suggest that ageing reduces the ability of fast muscles to increase myogenin protein levels, and prevents both fast and slow muscles from increasing MyoD protein levels during muscle unloading. Experimental Physiology (2001) 86.4, 509-517.

We examined the effect of time after birth and β3-adrenergic agonist (Zeneca D7114) administration on uncoupling protein-1 (UCP1) abundance and thermoregulation in the lamb. Forty twin lambs, all born normally at term, were maintained at a cold ambient temperature of between 3 and 8 °C. At 0.5, 1.75, 5.25, 11.25 and 23.25 h after birth eight sets of twins were fed 20 ml of formula milk ± 10 mg kg-1 of β3-adrenergic agonist, and 45 min after feeding brown adipose tissue (BAT) was sampled. Colonic temperature was measured and BAT analysed for UCP1 abundance, GDP-binding to mitochondrial protein (i.e. thermogenic activity) and catecholamine content. Colonic temperature declined between 1.25 and 6 h from 40.2 °C to 39.2 °C and then increased to 39.8 °C at 12 h, but increased after feeding at all ages. UCP1 abundance increased from 1.25 h after birth, to peak at 2 h after birth in controls, compared with 6 h after birth in β3-adrenergic agonist-treated lambs. The level of GDP-binding to mitochondrial protein did not change significantly with age but was increased by β3-adrenergic agonist treatment. The noradrenaline (norepinephrine) content of BAT increased between 1.25 and 12 h after birth, irrespective of β3-adrenergic agonist administration. The total weight of perirenal BAT plus its lipid, protein and mitochondrial protein content declined over the first 6 h of life. UCP1 development continues over the first 24 h of neonatal life, and can be manipulated by β3-adrenergic agonist administration. This may represent one method of improving thermoregulation in newborn lambs. Experimental Physiology (2001) 86.1, 65-70.

This study investigated if prior eccentric contractions, and thus mechanical strain and muscle damage, exert an effect on the muscle membrane phospholipid fatty acid composition in rats, and whether a possible effect could be attenuated by dietary supplements. Twenty-three rats were randomised to three groups who received chow with added fish oil (n = 8), vitamin C (n = 8) or no supplement (n = 7). After 3 weeks of feeding, calf muscles on one side were stimulated electrically during anaesthesia causing eccentric contractions. Two days later the white gastrocnemius, a part of the stimulated calf muscle, was excised from both legs. In the muscles stimulated to contract eccentrically, compared to the control muscles, the proportion of arachidonic acid, C20:4,n-6 (17.7 ± 0.6; 16.4 ± 0.4 % of total fatty acids, respectively) and docosapentanoeic acid, C22:5,n-3 (2.9 ± 0.1 and 2.7 ± 0.1 % of total fatty acids, respectively) was uniformly higher across groups (P < 0.02) with no differences between diet groups. The proportion of long chain polyunsaturates was also significantly higher in the eccentrically contracted (39.9 ± 0.6 % of total fatty acids) compared to the control leg (38.2 ± 0.6 % of total fatty acids; P < 0.01). In contrast no differences were observed in the fatty acid composition of the triacylglycerols stored within the muscle. Thus one severe bout of eccentric contractions modulates the fatty acid composition of the muscle membrane phospholipids when compared to a control leg, and supplemental intake of fish oil or vitamin C did not attenuate this effect. Experimental Physiology (2001) 86.5, 599-604.

Very brief and intense exercise triggers a biphasic metabolic and respiratory response with a second phase that occurs after the cessation of the muscular activity. The effects on minute ventilation (V˙E) produced by manipulation of the peripheral circulation in metabolically active muscles could thus be studied without the confounding effects of painful contractions. The second phase of breath-by-breath V˙E and pulmonary gas exchange responses to a brief change in work rate (400 W for 12 s) were studied in six healthy male subjects on four occasions (24 tests). An upper thigh cuff inflation was randomly applied either above or below the systolic blood pressure (200 or 90 Torr, respectively) for 90 s just after the cessation of the contractions prior to the delayed rise in pulmonary gas exchange (eight tests in each subject). Total occlusion produced a significant reduction in the delayed rise in V˙E (-29 ± 3 %) which normally occurred 20-25 s after the cessation of the contractions. In contrast, cuff inflation at a level predominantly impeding venous return while partially maintaining the arterial supply reduced the rise in pulmonary gas exchange in similar proportion to that during total obstruction but with a slight but not significant reduction in ventilation (-9 ± 5 %). V˙E during partial occlusion was if anything higher than in control tests with similar oxygen uptake (280 W), despite a higher blood pressure (BP) during occlusion (+7 Torr). It is concluded that the factors resulting from a reduction in venous return or from the involvement of the arterial baroreflex are not responsible for the changes in V˙E produced by the obstruction of the circulation to and from metabolically active muscles. It is proposed that factors related to the level of the perfusion pressure in hyperaemic muscles, possibly located at the venular end of the microcirculation, could account for the changes in V˙E observed. Experimental Physiology (2001) 86.6, 759-768.

This study was performed to determine whether the absorption of liquid from the lungs of postnatal sheep is dependent on pulmonary perfusion pressure, blood gases or blood flow. Relationships between perfusion pressure, rate of lung liquid absorption and perfusate PO2, PCO2 and pH were examined by linear regression analysis from in situ perfused lungs from sheep aged 6 weeks to 6 months. The airspaces of the lungs were filled with liquid containing an impermeant tracer, to allow measurement of the rate of liquid absorption. There was no significant relationship between the rate of lung liquid absorption and pulmonary blood flow (n = 36, r = -0.01, P > 0.1), pulmonary perfusion pressure (n = 36, r = 0.28, P > 0.05) or perfusate PO2, PCO2 or pH. No significant relationships were found between pulmonary blood flow and perfusate PO2, PCO2 or pH. There was no evidence to suggest that the absorption of liquid from the lungs of postnatal sheep is dependent on pulmonary blood flow, blood gases or perfusion pressure, within the limits studied, indicating that lung liquid absorption is dependent on the pulmonary epithelium and not on the pulmonary vasculature. The findings that lung liquid absorption continues in hypoxic environments and despite severe reductions in blood flow may be relevant to the field of transplant surgery. Experimental Physiology (2001) 86.3, 391-398.

Previous studies in fetal sheep have concluded that (a) the vascular AT1 angiotensin II (Ang II) receptor subtype is present in the external umbilical artery, but not in other systemic blood vessels, and (b) carotid arterial rings contract in vitro in response to Ang II. These contractions are blocked by the AT1 specific receptor antagonist losartan. The aim of the present study was to resolve the apparent contradiction of these earlier conclusions, by examining the distribution of Ang II receptor subtypes in different regions of the ovine fetal cardiovascular system, and to find out at what stage in development AT1 receptors first appear. We measured AT1 and AT2 receptors in hearts, carotid arteries, aortae and umbilical vessels from fetal sheep aged 65-144 days (term ~150 days), and in hearts and aortae from lambs, and adult pregnant and non-pregnant ewes. Both AT1 and AT2 receptors were present in aortae of fetuses > 118 days gestation, and carotid arteries of fetuses > 121 days gestation, while in younger fetuses only AT2 receptors were found. The proportion of carotid artery and aortic AT1 receptors increased with age, while the proportion of AT2 receptors decreased. The internal umbilical artery contained both subtypes, but there was no relationship between receptor density and gestational age. The external umbilical artery had only AT1 receptors. The highest density of Ang II receptors was found in the fetal heart where the AT2 subtype predominated. The density of fetal cardiac Ang II receptors declined with age (r = -0.44, P < 0.02) due to the decrease in the AT2 subtype. The density in late gestation fetal hearts was greater than in lamb or adult hearts (P < 0.001). Our study shows that fetal systemic blood vessels contain AT1 receptors, and we have documented for the first time that the appearance of AT1 receptors is both different in different regions of the fetal cardiovascular system and is developmentally regulated. Together with the in vitro contractile studies, this suggests that Ang II can play an important role in fetal blood pressure regulation via AT1 receptors in the fetal systemic vasculature, as well in the umbilicoplacental vessels. Experimental Physiology (2001) 86.1, 71-82.

Normal rats or rats parasympathetically denervated on one side by cutting the auriculo-temporal nerve were maintained on a liquid diet for 1 week. After fasting overnight, experimental rats were then offered hard, pelleted food over a period of 2 h, while unfed animals served as controls. The reflex-induced increase in the [3H]leucine incorporation into trichloroacetic acid-insoluble material of the parotid glands following intake of the food in the presence of the muscarinic blocker atropine and α- and β-adrenoceptor antagonists was greater (104 %) than in the absence of the blockers (75 %) in normal rats. The picture was the same when the innervated glands of rats subjected to unilateral parasympathetic denervation were examined. In this case, the protein synthesis increased by 108 % in the presence of the blockers and by 63 % in their absence. Analysis of the parasympathetically denervated and contralateral innervated glands revealed no support for a cholinergic or adrenergic contribution to this response. The increase in protein synthesis in the innervated glands was 86 % in the rats treated with atropine, whilst it was 76 % in those treated with α- and β-adrenoceptor antagonists. The protein synthesis in the denervated glands increased by 57 % in the absence of receptor blockade. Neither atropine (51 %), nor a- and b-adrenoceptor antagonists (52 %), nor a combination of the three blockers (55 %) affected the response of the denervated glands. A large part of the response in the presence of the traditional autonomic receptor blockers was thus dependent on the parasympathetic auriculo-temporal nerve. Under natural feeding conditions, the parasympathetic non-adrenergic, non-cholinergic (NANC) mechanisms are likely to contribute to the synthesis of secretory proteins. Experimental Physiology (2001) 86.5, 605-610.

The Physiological Society hosts a number of Special Interest Groups whose task it is to foster lively debate among members within a specific area of topical research. Inevitably there are many topics that straddle these sometimes arbitrary divides where fresh understanding may be derived from two or more groups focussing attention on a specific topic. Vagal control of the cardiovascular system is a good example where an exchange of ideas may be of mutual benefit among the Comparative section (utilising the diversity of form resulting from natural selection) and the Cardiovascular/Respiratory Control section (concentrating on the intricacies of the mammalian system). The title of the joint symposium held at the Oxford meeting recognised the evolutionary theme that was used to highlight the various patterns of sympathetic control that are found among the vertebrates. The first contribution highlights the presumptive ancestral nature of vagal control, where it predated sympathetic innervation of the heart (Taylor et al., pp. 771-776). The role of the vagus in unusual situations is examined by use of examples from periodic feeding in reptiles (Wang et al., pp. 777-784), cardiac shunting in crocodiles (Axelsson, pp. 785-789), and diving bradycardia in birds (P. J. Butler, delivered at the meeting but not included here). The central role of the vagus in mammalian homeostasis is emphasised with respect to hibernation (Milsom et al., pp. 791-796), while complexities of the mammalian system are illustrated by the rat heart (Jones, pp. 797-801) and perinatal development in lambs (Lalani et al., pp. 803-810). We conclude with overviews of the controversies in human studies regarding vagal control during exercise (Coote & Bothams, pp. 811-815) and its utility in the clinical setting (Casadei, pp. 817-823). We hope this collection of short articles will help stimulate further debate and interaction. Experimental Physiology (2001) 86.6, 769-769.

STUART EGGINTON Convenor, Comparative Special Interest Group

TERESA THOMAS Convenor, Cardiovascular/Respiratory Control Special Interest Group

Viscoelastic properties determine the dynamic behaviour of the arterial wall under pulsatile pressure and flow, suggesting time- or frequency-dependent responses to changes in wall stress and strain. The objectives of the present study were: (i) to develop a simplified model to derive simultaneously the elastic, viscous and inertial wall moduli; (ii) to assess Young's modulus as a function of frequency, in conscious, chronically instrumented dogs. Parametric discrete time models were used to characterise the dynamics of the arterial system based on thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements in control steady state and during activation of smooth muscle with the α-adrenoceptor agonist phenylephrine (5 µg kg-1 min-1, I.V.), in eight conscious dogs. The linear autoregressive model and a physically motivated non-linear model were fitted to the input-output (stress-strain) relationship. The aortic buffering function (complex Young's modulus) was obtained in vivo from the identified linear model. Elastic, viscous and inertial moduli were significantly increased from control state ((44.5 ± 7.7) × 104 Pa; (12.3 ± 4.7) × 104 Pa s; (0.048 ± 0.028) × 104 Pa s2 ) to active state ((85.3 ± 29.5) × 104 Pa, P < 0.001; (22.4 ± 8.3) × 104 Pa s, P < 0.05; (0.148 ± 0.060) × 104 Pa s2, P < 0.05). These moduli, obtained using the linear model, did not present significant differences compared with those derived using the non-linear model. In control conditions, the magnitude of the normalised complex Young's modulus was found to be similar to that reported in previous animal studies ranging from 1 to 10 Hz. During vascular smooth muscle activation, this modulus was found to be increased with regard to control conditions (P < 0.01) in the frequency range used in this study. The frequency-dependent Young's modulus of the aortic wall was obtained for the first time in conscious, unsedated dogs. The parametric modelling approach allows us to verify that vascular smooth muscle activation increases the elastic, viscous and inertial moduli with the advantage of being able to track their time evolution. Furthermore, under activation, the aortic wall remains stiff in the physiological frequency range, suggesting the impairment of the arterial buffering function. Experimental Physiology (2001) 86.4, 519-528.

This issue contains a number of papers based on presentations from a Uterine Contractility Symposium held in Oxford, UK on May 3rd, 2000. They represent an overview of current knowledge on the regulation of uterine smooth muscle. Research in this area is important because disorders of parturition, notably preterm labour, remain a major cause of perinatal mortality and carry a wide range of short- and long-term morbidity in the surviving infants. Available therapies are inefficient or have undesirable side effects for the mother or the baby. A better understanding of the physiology of parturition and the cellular basis of uterine contractility will lead to the development of more efficacious and selective drugs for the management of preterm labour and other disorders of uterine function. The main presentation was the Litchfield Lecture (sponsored by the Medical School), which was given by Professor Barbara Sanborn. There were also presentations of very high standard by scientists and clinicians with a long-standing interest in this subject, and by young scientists. I am most grateful to all the contributors for their enthusiasm and for making an effort to produce quality manuscripts as a scientific record of this symposium. All the manuscripts have been fully reviewed and I am particularly indebted to Professor Lucilla Poston for coordinating the editorial work. The symposium was supported by educational grants from the Serono Pharmaceutical Research Institute, GlaxoWellcome R&D, Alliance Pharmaceuticals, Ferring Pharmaceuticals, Unipath and Aventis Pharma.

The aim of this study was to investigate the role of the parasympathetic (cholinergic and peptidergic) nervous system in the regulation of exocrine pancreas function in piglets during their early postnatal development. The cholinergic and peptidergic regulatory pathways of exocrine pancreatic function were tested by the specific muscarinic receptor blocker 4-diphenylacetoxy-N-methylpiperidine-methiodide (4-DAMP) and bombesin, respectively. At the age of 2 weeks, piglets were surgically fitted with a chronic pancreatic duct catheter, a duodenal re-entrant cannula and a jugular vein catheter. The experiments comprised a pre-weaning period, and a post-weaning period that commenced at the beginning of the 5th week of age. Intravenous infusion of 4-DAMP (100 pmol kg-1 h-1) reduced the outflow of pancreatic juice, the output of total protein and the activity of trypsin, chymotrypsin, carboxyl ester hydrolase and amylase during preprandial and postprandial pancreatic secretion, in both the pre- and post-weaning periods. However, the inhibitory effect of 4-DAMP during postprandial secretion was significantly greater (P < 0.05) in suckling piglets. The infusion of bombesin (10, 100 and 1000 pmol kg-1 h-1) stimulated exocrine pancreatic secretion in a dose-dependent manner during both the pre- and post-weaning periods. However, the stimulatory effect of 1000 pmol kg-1 h-1 bombesin on total protein output and the activities of trypsin, chymotrypsin and amylase were significantly higher (P < 0.05) in suckling piglets. In summary, our study showed that cholinergic and peptidergic mechanisms are involved in the regulation of exocrine pancreas function in piglets in both the pre- and post-weaning stages. 4-DAMP had a greater inhibitory effect on exocrine pancreatic secretion in piglets during the pre-weaning period. Thus, these observations suggest that the parasympathetic nervous system plays a dominant role in the functioning of the exocrine pancreas at this time. The action of bombesin suggests that it is a potent secretagogue for the exocrine pancreas in pigs during their postnatal development. Experimental Physiology (2001) 86.3, 399-409.