Changes In Respiratory Activity Research Articles

α 2 Adrenergic receptors and the central control of breathing in the cane toad, Bufo marinus

The effect of adrenergic agents on the central control of breathing in the cane toad, Bufo marinus, was tested by applying adrenergic agents to the ventral medullary surface of decerebrate adult toads. Toads were unidirectionally ventilated while recording lung, buccal, and artery blood pressures (BPI), as well as heart rate (HR). Following a control period, filter paper pledgets soaked in the appropriate solution (epinephrine — 0.023, 0.05, 0.10, and 0.23 mM; norepinephrine — 0.002, 0.016, 0.032, and 0.16 mM; clonidine — 0.00375, 0.0375, and 0.375 mM; or yohimbine — 0.43) mM) were placed bilaterally on the ventral medullary surface. Epinephrine significantly increased the number of breaths (26%), lung amplitude (9%), and episode duration (21%), but had no effect on BP or HR. The α 2-agonist. clonidine, significantly increased respiratory activity at moderate doses (0.0375 mM) and decreased activity at high doses (0.375 mM), however, it failed to elicit significant changes in BP or HR. Pretreatment with the α 2-adrenoceptor antagonist, yohimbine (0.43 mM), blocked the clonidine induced changes in respiratory activity. Yohimbine had no effect on cardiorespiratory parameters. Norepinephrine had no effect on either cardiovascular or respiratory variables. Thus, it appears that an α 2 adrenergic mechanism is involved in the central control of respiration in this lower vertebrate.

Serotonergic modulation of respiratory neural activity during tadpole development

The respiratory physiology of bullfrogs undergoes important modifications during development [1,2,3]. The dramatic changes in the partitioning of gas exchange function between lungs and gills during development require important alterations in the neural mechanisms controlling ventilation [4,5]. Yet, the mechanisms at the basis of these changes in respiratory motor behaviour remain poorly understood. Hilaire and Duron proposed that maturation of the mammalian respiratory network may be defined, at least partly, by serotonergic modulatory processes [6]. To test the hypothesis that serotonergic modulation of respiratory neural activity changes during tadpole development, the effects of serotonin (5-HT) on neural correlates of respiratory activity were assessed using an in vitro brainstemspinal cord preparation. Preparations from tadpoles of developmental stages varying between TK stagesVI and XXV were superfused with mock CSF containing 5-HT concentrations ranging from 0–25 μM. Neural correlates of gill and lung ventilation were recorded extracellularly from cranial nerve rootletsV andX. In younger tadpoles (facultative air breathers; TK stages VI-XV) 5-HT bath application attenuated the frequency and amplitude of respiratory-related motor output (both fictive gill and lung ventilation), an effect most notable at high concentrations. In more mature animals (obligate air breathers; TK stages XVI-XXV), the effects of 5-HT bath application on fictive lung ventilation was bi-phasic. Fictive lung ventilation frequency was enhanced at low 5-HT concentrations (0.5 μ) and was depressed by higher 5-HT concentration. Moreover, 5-HT-induced attenuation of fictive gill ventilation was stronger in obligate air breathers than in preparations from younger tadpoles. These results indicate that serotonergic modulation of respiratory activity changes substantially during tadpole development. Such changes in modulatory influences may contribute to the maturation of the respiratory control system in this species.

Respiratory neural activity responses to chemical stimuli in newborn rats: reversible transition from normal to 'secondary' rhythm during asphyxia and its implication for 'respiratory like' activity of isolated medullary preparation.

To clarify a possible origin of 'respiratory like' rhythmic activities observed in in vitro brainstem preparation, the phrenic (Phr) and cranial nerve (XII or IX) inspiratory activities were analyzed in halothane-anesthetized, vagotomized and artificially ventilated newborn (2--6 days after birth) and young adult rats (30--50 days) during altered chemical stimuli and prolonged asphyxia at 25 degrees C. The newborn rat showed regular rhythmic inspiratory discharges of short duration, and their responses to CO(2) and hypoxia did not differ from those seen in adult rats. In the newborn rat the Phr and cranial nerve inspiratory discharges increased first, then respiratory frequency decreased and finally ceased completely for approximately 1--2 min during asphyxia. Thereafter, 'secondary' rhythmic inspiratory activity emerged at a slower rate with decremental inspiratory discharge profile, which persisted for a period more than 40 min of asphyxia. A normal respiratory activity recovered after resumption of artificial ventilation. Though young adult rats exhibited similar sequential changes in respiratory activity during asphyxia, the 'secondary' rhythmic activity persisted for a period of several min only. The pattern of 'secondary' respiratory activity corresponded well with that of rhythmic activities seen in the isolated medullary block preparation of newborn rat. 'Respiratory like' activity found in isolated medullary preparations of newborn animals may arise from a mechanism that generates 'secondary' (or so called 'gasping' type) rhythmic inspiratory activity during prolonged asphyxia in in vivo preparations.

Sensing arterial CO 2 levels: a role for medullary P2X receptors

ATP has been shown to act as an excitatory neurotransmitter in the central nervous system. In this review, evidence is presented to indicate that when ATP is micro-injected into the ventrolateral medulla (VLM) of the rat, changes in respiratory activity are elicited. These effects, and accompanying changes in heart rate and blood pressure are mediated by P2X purinoreceptors. Immunocytochemistry indicates a prevalence of P2X 2 and P2X 6 purinoreceptors in this region of the medulla. The P2 purinoceptor antagonists, suramin and PPADS blunt the respiratory responses to changes in arterial CO 2 levels when micro-injected into the VLM. This effect is shown electrophysiologically to be mediated by purinoreceptors located primarily on respiratory neurones of the VLM including the Bötzinger complex. As the effects of agonist activation of P2X 2 purinoceptors expressed in HEK293 cells and Xenopus oocytes are potentiated by lowering pH, these data imply that the central respiratory response to CO 2 depends in part on the pH sensitivity of purinoreceptors located on inspiratory neurones. The implications for respiratory activity and control are discussed.

Impairment of brain mitochondrial function by hydrogen peroxide

Hydrogen peroxide, at concentrations comparable to those observed under some pathological conditions, produced a concentration-dependent inhibition of state 3 (ADP-stimulated) and uncoupled mitochondrial respiratory activity. The ADP:O ratio was also substantially reduced. In contrast, the organic peroxide, t-butylhydroperoxide at the same concentrations produced no significant changes in respiratory activity. Intramitochondrial glutathione was oxidised to a similar extent in the presence of hydrogen peroxide or t-butylhydroperoxide. Thus, changes in this endogenous antioxidant apparently did not underlie the different responses to these peroxides. The effects of hydrogen peroxide were not altered by deferoxamine indicating that the extramitochondrial generation of hydroxyl radicals was not likely to be involved. However, modifications arising from the generation of hydroxyl radicals within the mitochondria remain a likely contributor to the observed deleterious effects on respiratory function. The inhibitory effects of hydrogen peroxide were greatest when pyruvate plus malate were present as respiratory substrates. Lesser inhibition was seen with glutamate plus malate and no significant inhibitory effects were detected in the presence of succinate. The findings suggest that mitochondrial components involved in pyruvate oxidation were particularly sensitive to the hydrogen peroxide treatment. However, no significant change was seen in activity of either the pyruvate dehydrogenase complex or NADH–ubiquinone oxidoreductase (complex I) when measured directly following treatment of the mitochondria with hydrogen peroxide.

Role of glutamate receptor subtypes in the lamprey respiratory network

The respiratory role of glutamate receptors was investigated in the isolated lamprey brain preparation by analyzing the changes in respiratory activity induced by bath application of specific antagonists of ionotropic and metabotropic glutamate receptors. The results show that these antagonists differentially affect the pattern of breathing and provide the first evidence that both ionotropic and metabotropic glutamate receptors are involved in neurotransmission within the lamprey respiratory network.

The coordination and interaction between respiration and deglutition in young pigs.

The anatomical pathways for inspired air and ingested food cross in the pharynx of mammals, implying that breathing and swallowing must be separated either in space or in time. In this study we investigated the time relationship between swallowing and respiration in young pigs, as a model for suckling mammals. Despite the high morphological position of the larynx in young mammals, allowing liquid to pass in food channels lateral to the larynx, respiration and swallowing are not wholly independent events. Although, when suckling on a veterinary teat, the swallows occurred at various points in the respiratory cycle, there was always a period of apnea associated with the swallow. Finally, an increase in the viscosity of the milk altered this coordination, changing respiratory cycle length and also restricting the relative rate at which swallows occurred in some parts of the respiratory cycle. These results suggest that the subsequent changes in respiratory activity at weaning, associated with passage of a solid bolus over the larynx, is preceded by the ability of the animal to alter coordination between respiration and swallowing for a liquid bolus.

Effect of nitric oxide on the respiratory activity generated under hypoxic conditions by medullo-spinal preparations from early postnatal rats

Experiments on superfusedin situ semi-isolated medullo-spinal preparations (SIMSP) of 3- to 4-day-old rats were carried out to study the effects of a blocker of nitric oxide synthase (NO synthase), methyl ester of NG-nitro-L-arginine (MENA), and an exogenic NO donor, nitroglycerin, on the respiratory activity. Inspiratory discharges (ID) were recorded from the phrenic nerve under superfusion of SIMSP with a standard saline and a solution saturated with anoxic isocapnic gas mixture. Under normal conditions, 3-min-long applications of 1.0 μM MENA evoked no significant changes in the parameters of inspiratory activity; yet 10.0 μM of this blocker evoked a significant drop in the amplitude and an increase in the ID frequency. Three-min-long applications of 1.0 μM nitroglycerin significantly decreased the ID frequency and somewhat increased their amplitude and integral intensity. Higher doses of nitroglycerin (10.0 μM) significantly increased the amplitude and integral intensity of ID and in a lesser extent lowered their frequency. Under conditions of 3-min-long hypoxia, 10-min-long preliminary superfusion of SIMSP with the 1.0 μM MENA-containing saline resulted in no significant changes of respiratory activity, as compared with the hypoxia effect in the norm. Applied before the hypoxic test, 10 μM MENA resulted in significant decreases in the amplitude and integral intensity of ID; concurrently their frequency became higher, as compared with the respective parameters measured at hypoxic testing of the intact preparations. Ten-min-long superfusion with 1.0 μM nitroglycerin-containing solution at subsequent hypoxic testing significantly increased the amplitude and integral intensity of ID and decreased their frequency; these shifts developed during the first half of exposure to the hypoxic solution. Increased (to 10 μM) nitroglycerin concentration resulted in less intensive shifts in the ID frequency within the first half of a hypoxic episode. In a part of the tests, the second half of exposure of SIMSP to the hypoxic solution was characterized by the appearance of low-amplitude short ID against the background of suppressed eupnea-like respiratory activity; we qualified such discharges as gasping discharges. The experimental data confirm the involvement, of NO in the central regulation of the frequency and amplitude parameters of inspiratory activity generated by SIMSP of early postnatal rats both under normoxic and hypoxic conditions. The role NO plays under hypoxic conditions in modifications of parameters of respiratory activity and in modulation of the functional, levels of the bulbar respiratory generator is discussed.

Introduction to papers from the GAP VI workshop: effects of physical forcing on primary production processes in inland and marine environments

The Group for Aquatic Primary Productivity (GAP) was established in 1980 at the Societas Internationalis Limnologiae’s (SIL) 21st Congress in Kyoto, Japan. GAP is a working group of both SIL and INTECOL (The International Association of Ecology) and is run by an international committee composed of seven scientists from Australia, Canada, Denmark, France, Israel, Japan, and the United States. The purpose of GAP is to assess the state of knowledge on a wide range of topics related to marine and freshwater primary production, to perform joint field and laboratory experiments using different techniques to test their comparability and reliability, to define major knowledge gaps and urgent research needs, and to publish these results in international journals. To carry out its mandate, GAP holds workshops approximately every 3 years, and each workshop addresses a specific theme. In addition, GAP also convenes smaller ad hoc workshops to address a specific issue or to investigate a regional aspect of primary production. An example of the latter was the investigation of the warm-core Cyrus Eddy in the Levantine Basin of the eastern Mediterranean Sea, organized by Tom Berman of the Israel Oceanographic and Limnological Research Ltd. GAP depends upon proposals from interested scientists, who volunteer themselves and an organizational team and their institutions to organize and host workshops. Past workshops have been held in several European countries and Israel, and results have been published in several journals. In 1993, GAP VI was held at Environment Canada’s National Hydrology Research Institute in Saskatoon, Saskatchewan, a location that provided easy access to a wide variety of saline lakes and to the South Saskatchewan River. The theme of GAP VI was “Effects of physical forcing on primary production processes in inland and marine environments.” The global concerns about the depletion of the ozone layer and the effects of increased ultraviolet (UV) radiation on aquatic systems resulted in many of the GAP VI participants examining this topic. Four papers containing data produced during GAP VI appear in this issue of the Canadian Journal of Fisheries and Aquatic Sciences. Each paper was reviewed by two or three referees before being accepted for publication. I thank these referees for their time and interest in helping the authors prepare their final manuscripts. Beardall et al. reported changes in respiratory activity and photosynthetic carbon assimilation of a cyanobacterium and a green alga when exposed to different levels of photosynthetically active radiation (PAR) and UV-A + UV-B radiation. The organisms differed in their responses, which led Beardall et al. to conclude that there is considerable interspecific variation in the response of autotrophic organisms to UV radiation and these responses are modulated by the level of concomitant exposure to PAR. Information on UV radiation effects on the plankton of prairie saline lakes in Canada is lacking. Two studies were conducted with water from Redberry Lake, an oligotrophic saline lake. Maske and Latasa presented data on changes in phytoplankton pigment content, and suggested that environmental factors other than UV-B, or the state of cellular adaptation, partially controlled reduction of pigment. Ferreyra et al. measured the effects of UV-B on phytoplankton carbon assimilation, chlorophyll a concentration, bacterial numbers, and bacterial electron transport system activity, and found different responses to UV-B in these two groups of organisms. In addressing the major GAP objective of conducting methodological comparisons, Bott et al. worked in the South Saskatchewan River to compare four methods to measure periphyton metabolism in in situ chambers. As a result of this research the authors were able to make recommendations for future research that is needed when measuring periphyton metabolism in chambers. GAP workshops offer an unique opportunity for aquatic scientists to come together in short-lived, tightly focused teams and effectively address key research questions, as demonstrated by these papers from GAP VI.

Extension rate and respiratory activity in the growth zone of wheat roots: Time‐course for adjustments after defoliation

The time‐course for adjustments in the rate of extension of wheat (Triticum aestivum L. cv. Alexandria) roots, and the activity and capacity of respiratory pathways in the root apex, were determined after pruning the shoot to the ligule of the first leaf. Leaf pruning reduced the extension rate of both seminal and lateral roots. The onset of the response occurred within 1 h of pruning for laterals and between 2 and 3 h for seminals. The reduction in rate appears to be the result of a decrease in carbohydrate availability because (1) in seminal roots it was preceded by a decrease in soluble sugar content of the apical part of the growth zone (0–5 mm behind the root apex) and (2) supplying glucose (50 mM) to the roots of plants defoliated 24 h earlier led to a steady increase in extension rate of both seminal and lateral roots compared to non‐fed controls. Supplying 3‐O‐methyl glucose had no effect. The reduction in extension rate of seminal roots was accompanied (or slightly preceded) by a reduction in respiratory O2 uptake in the apical part of the growth zone (0–5 mm). Changes in respiratory activity in the basal part of the growth zone (5–10 mm) only occurred several hours later. At the time root extension rate was reduced, the rate of O2 uptake could be stimulated with FCCP, which indicates that respiration was under the fine control of adenylates. From these results we suggest the following sequence of events occurs after defoliation. Firstly, defoliation reduces the supply of sugars to the root apex, this leads to a reduction in rate of extension through some form of coarse control by carbohydrates on cell division and expansion, which in turn reduces the rate of respiratory O2 uptake because of a smaller demand for ATP. The results also indicate that there is a rapid (<1.5 h) reduction in respiratory capacity in the root apex after defoliation which occurs before any change in the overall rate of respiration.

A Strategy for the Evaluation of Sensory and Pulmonary Irritation Due to Chemical Emissions from Indoor Sources.

Sensory and pulmonary irritation are physiological responses to chemical exposure which result in characteristic, measurable changes in respiratory activity in mice. A standard method has been applied to the estimation of sensory irritation associated with a specific chemical exposure. This method has been correlated with human responses to these chemicals. Symptoms associated with chemical irritants are consistent with complaints due to problems with indoor air quality, which may include eye and upper respiratory tract irritation, headaches, and nausea. A stepwise strategy for assessing the contribution of indoor products to sensory and pulmonary irritation is discussed in the current paper. The strategy includes product emissions testing using dynamic environmental chambers, the selection of suspected irritants for respiratory irritation testing, respiratory irritation testing of individual compounds and representative mixtures using synthesized atmospheres, and the evaluation of test data to determine those compounds which may contribute to sensory and pulmonary irritation in humans. The current strategy is being applied to evaluate carpet system materials and their constituent chemicals.

Perinatal developmental changes in respiratory activity of medullary and spinal neurons: an in vitro study on fetal and newborn rats

Experiments were performed in vitro on fetal and newborn rat brainstem-spinal cord preparations to analyse the perinatal developmental changes in inspiratory motor output. The amplitude of the inspiratory bursts of the whole C4 ventral root (global extracellular recording), the firing patterns of 80 medullary inspiratory neurons (unitary extracellular recording) and the firing and membrane properties of 71 respiratory neurons in the C 4 ventral horn (whole-cell recording) were analysed at embryonic day 18 (E18), 21 (E21) and post natal days 0 to 3 (P0–3). At E18, the amplitude of the C 4 bursts was weak and variable from one respiratory cycle to the next, as well as the discharge pattern of most of the medullary inspiratory neurons. C 4 motoneurons were immature, very excitable and displaying variable inspiratory discharges, but already able to deliver sustained bursts of potentials when depolarised. At E21 and P0–3, the amplitude of the C 4 bursts was increased and stable, most of the medullary inspiratory neurons already were able to generate a stable firing pattern and C 4 motoneurons showed maturational changes in terms of the resting potential, spike amplitude and input membrane resistance. This work suggests that the short period extending from E18 to E21 is a critical maturational period for the medullary respiratory network which becomes able to elaborate a stable respiratory motor output.

Further evidence that various 5-HT receptor subtypes modulate central respiratory activity: in vitro studies with SR 46349B

The ability of SR 46349B { trans,4-([3 Z)3-(2-dimethylaminoethyl)oxyimino-3(2-flurophenyl)propen-1-yl]phenol hemifumarate}, a 5-HT 2 receptor antagonist, to block the changes in respiratory activity induced by serotonin was analysed by using brain stem-spinal cord preparations from newborn rats. The increases in respiratory frequency elicited by serotonin (and 5-HT 1A receptor agonist) were not suppressed by SR 46349B. The tonic discharge of cervical motoneurons and the depression of inspiratory hypoglossal activity elicited by serotonin (and 5-HT 2 receptor agonist) were reduced in a dose-dependent manner by SR 46349B. These results confirm that activation of 5-HT 1A and 5-HT 2 receptors influences respiratory frequency and motoneuronal output, respectively.

Effect of activation of 5-HT 1A receptors at the ventral medulla on phrenic nerve activity

The purpose of this study was to determine the effects of the 5-HT 1A receptor agonist, 8-hydroxy-2-(di- N-propylamino)tetralin hydrobromide (8-OH-DPAT), on respiratory activity (phrenic nerve activity) following application to the ventral medullary surface in the cat. In addition, in order to determine if the action of 8-OH-DPAT was localized to structures at the ventral medulla, we examined the distribution of [ 3H]8-OH-DPAT to other brain regions and to the peripheral circulation. 8-OH-DPAT (0.0625–0.0628 μg) produced a dose-related increase in respiratory rate when applied at either the intermediate or caudal areas on the ventral surface of the medulla. The maximal change in respiratory rate was 9 ± 2 and 8 ± 1 breaths/min at the intermediate and caudal areas, respectively. Integrated phrenic nerve amplitude was not significantly affected at these sites except at the 8 μg dose where it was decreased. No change in phrenic nerve activity was observed with 8-OH-DPAT application at the rostral area. [ 3H]8-OH-DPAT was not found to distribute to other brain regions or to the peripheral circulation following application to the ventral medullary surface. The results of this study suggest that 8-OH-DPAT causes changes in respiratory activity, primarily respiratory rate, by acting on neuronal structures at the ventral surface of the medulla.

Changes in dormancy of Sisymbrium officinaleseeds do not depend on changes in respiratory activity

Effects of dark incubation at different temperatures were studied on dormancy and respiratory activity of seeds of Sisymbrium officinale (L.) Scop. Because germination of this species absolutely depends on the simultaneous action of light and nitrate, changes in dormancy could be studied in darkness without the interference of early germination events. Upon the start of incubation rates of O2 uptake and CO2 release rose. This was followed by a gradual decrease until stable levels of O2 uptake and CO2 release were achieved. Seeds kept for prolonged periods at 24°C, showed neither a change in germination capacity nor in rates of O2 uptake and CO2 release. Respiratory quotients were 0.55–0.7. The initial rise in O2 uptake correlated with the rate of water uptake and with breaking of primary dormancy. However, the subsequent decline in O2 uptake was not generally linked to induction of secondary dormancy. An increased O2 uptake was not required during breaking of secondary dormancy. It is concluded that changes in dormancy are not generally related to changes in respiratory activity. However, germination strongly depends on respiration. The increase in O2 uptake started well before radicle protrusion. A far red irradiation only reversed this increase when it was given before germination escaped from its red light antagonising action. The contribution of different respiratory pathways was followed during prolonged incubation at 24°C in darkness. KCN at 1.5 mM was needed to inhibit the cytochrome pathway (CP) and benzohydroxamic acid (BHAM) at 30 mM to inhibit the alternative pathway (AP). These concentrations did not exert any side effects. Electron flow was predominantly via the CP, maximally 10% was via the AP. Flow through the CP declined during the first 6 days and residual respiration remained constant. Therefore, the contribution of residual respiration became relatively more important with prolonged incubation. KCN at concentrations that almost completely inhibited flow through the CP, did not dramatically reduce germination. BHAM already inhibited germination at concentrations that do not inhibit oxygen uptake.

Characterization of hindlimb muscle afferents involved in ventilatory effects observed in decerebrate and spinal preparations

Neurogenic changes of phrenic activity have previously been observed during periodic passive motions of one hindlimb in decorticate, unanaesthetized and curarized rabbit preparations before and after high spinal transection (Palisses et al. 1988). In decerebrate and spinal preparations, we aimed to determine, through rhythmic electrical stimulation of hindlimb muscle nerves, which muscle afferents are involved in these effects. In decerebrate preparations, these electrical stimulations (trains of shocks at 80 Hz for 300 ms every second for 20 s) produced ventilatory effects when group I + II afferent fibres of either flexor or extensor nerves were stimulated together and more powerful changes as soon as group III fibres were recruited. Stimulation of group I fibres alone induced no such effects. When present, these changes in respiratory activity consisted of a maintained decrease of the respiratory period due to both inspiratory and expiratory time shortening; in addition, the amplitude of the phrenic bursts greatly increased at the onset of electrical stimulation. After spinal transection at C2 level and pharmacological activation by nialamide and DOPA, only short-lasting phrenic bursts developed spontaneously; the electrical stimulation of group II and mainly group III flexor afferent fibres induced large amplitude phrenic activity whereas the stimulation of the same extensor afferents was relatively ineffective. The activation of phrenic motoneurones during group III flexor afferent stimulation was closely linked to each 300 ms period of stimulation. While the phrenic effects obtained in the spinal preparations by natural and by electrical periodic stimulation are quite similar to each other, those produced in decerebrate preparations differ substantially.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in respiratory activity induced by mastication in humans.

We studied the influence of mastication on respiratory activity in nine healthy volunteers who were requested to masticate a 5-g chewing gum bolus at a spontaneous rate (SR) for 5 min and "at the maximum possible rate" (MPR) for 1 min. Significant increases in respiratory frequency were induced by SR mastication due to a decrease in both the inspiratory and expiratory time. Tidal volume displayed slight nonsignificant decreases, but minute ventilation and mean inspiratory flow significantly increased. The duty cycle (TI/TT) did not change significantly. Total airway resistance significantly increased. Both peak and rate of rise of the integrated electromyographic activity of inspiratory muscles presented marked increases, accompanied by the appearance of a low level of tonic muscular activity. Similar but more intense effects on respiratory activity were induced by MPR mastication; in addition, a significant decrease in tidal volume and a significant increase in TI/TT were observed. Rhythmic handgrip exercise performed at metabolic rates comparable to those attained during SR or MPR mastication induced similar changes in the drive and time components of the breathing pattern, although accompanied respectively by nonsignificant or significant increases in tidal volume. Furthermore, the frequency of SR mastication significantly entrained the respiratory rhythm. The results suggest that mastication-induced hyperpnea does not merely represent a ventilatory response to exercise but also reflects complex interactions between respiratory and nonrespiratory functions of the upper airway and chest wall muscles.

Noradrenergic modulation of the medullary respiratory rhythm generator in the newborn rat: an in vitro study.

1. Superfused brain stem-spinal cord preparations of newborn rats, which continue to show a rhythmic respiratory activity in vitro, were used to analyse the mechanisms whereby the A5 noradrenergic area modulates the activity of the medullary respiratory rhythm generator in the newborn. 2. In preparations including the pons (ponto-medullary preparations), noradrenaline (NA, 25-100 microM) added to the bathing medium either increased (n = 29/50) or decreased (n = 21/50) the respiratory frequency and elicited a tonic discharge in the cervical ventral roots in 50% of the experiments. Double-bath experiments showed that the increases in respiratory frequency were due to NA acting on the pons, whereas the decreases in respiratory frequency were due to NA acting on the medulla. The NA-induced increases in respiratory frequency were attributed to inhibition of A5 neurons by NA and therefore to withdrawal of A5 inhibition on the medullary rhythm respiratory generator. The NA-induced decreases in respiratory frequency seemed to mimic the effects of endogenous NA on the A5 medullary targets. 3. Noradrenaline-induced tonic activity (i) could be induced after elimination of the pons but not on isolated spinal cord, (ii) could be elicited by alpha 1- but not alpha 2-agonists, (iii) could be blocked by alpha 1- but not alpha 2-antagonists. The tonic activity therefore originated from activation of alpha 1 receptors located in the medulla but its importance in respiratory function is doubtful. 4. In medullary preparations (elimination of the pons by transection), the effects of NA agonists and antagonists on respiratory frequency were analysed. Significant decreases in respiratory frequency were induced by NA, adrenaline, phenylephrine and alpha-methyl-NA, but not by the agonists classified as alpha 2 (clonidine and guanfacine), alpha 1 (6-fluoro-NA) and beta (isoprenaline). Since yohimbine, idazoxan and piperoxane (alpha 2 antagonists) blocked the NA-induced decreases in respiratory frequency whereas prazosin (alpha 1-antagonist) did not, it is postulated that alpha 2-receptors may be involved in modulating respiratory frequency. 5. Stimulation, lesion and NA microejection experiments showed the complexity of the mechanisms mediating NA-induced changes in respiratory activity but suggested that the main site of NA action is located in the rostral ventrolateral medulla, where electrical stimulations triggered inspiration prematurely, lesions suppressed the NA-induced decrease in respiratory frequency, and localized application of NA led to an immediate decrease in the respiratory frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of carbon source and oxidative metabolism on secondary metabolism inStreptomyces thermoviolaceus

The effect of carbon source on a number of cultural parameters was investigated inStreptomyces thermoviolaceus. Glucose-grown cultures produced the antibiotic granaticin during pH-controlled growth in a fermenter. Biphasic growth occurred for all the carbon sources tested at 45°C, the inflexion of which occurred at a biomass density of between 0.5 and 0.6 gL−1 and which coincided with the onset of appearance of secondary metabolites. Maximum antibiotic production occurred in proline-grown cultures, which also had the slowest growth rates during the secondary phase of growth. Respiratory chain activity was probed by measuring NADH oxidation in membrane preparations exposed to a range of cyanide concentrations. Modulation of the terminal oxidase activity was apparent so that membranes prepared from cultures in the antibiotic-producing phase were less sensitive to KCN than those prepared from the early exponential phase of growth. The probable reason for this difference was the synthesis of cytochrome oxidased during later stages of growth. These changes in respiratory activity are discussed in relation to patterns of growth and timing of the appearance of secondary metabolites synthesised byS. thermoviolaceus.

Kinetics of wheat straw solid-state fermentation with Trametes versicolor and Pleurotus ostreatus ? lignin and polysaccharide alteration and production of related enzymatic activities

The kinetics of straw solid-state fermentation (SSF) with Trametes versicolor and Pleurotus ostreatus was investigated to characterize the delignification processes by these white-rot fungi. Two successive phases could be defined during straw transformation, characterized by changes in respiratory activity, changes in lignin and polysaccharide content and composition, increase in in-vitro digestibility, and enzymatic activities produced by the fungi. Lignin composition was analysed after CuO alkaline degradation, and decreases in syringyl/guaiacyl and syringyl/p-hydroxyphenyl ratios and cinnamic acid content were observed during the fungal treatment. An increase in the phenolic acid yield, revealing fungal degradation of side-chains in lignin, was produced by P. ostreatus. The highest xylanase level was produced by P. ostreatus, and exocellulase activity was nearly absent from straw treated with this fungus. Lactase activity was found in straw treated with both fungi, but lignin peroxidase was only detected during the initial phase of straw transformation with T. versicolor. High levels of H2O2-producing aryl-alcohol oxidase occurred throughout the straw SSF with P. ostreatus.