Biomedical subjects

L Sundin

Publications and source records attributed to L Sundin.

At least 19 recordsLinked to original sources

PubMed2006

Late onset of NMDA receptor-mediated ventilatory control during early development in zebrafish (Danio rerio).

Increased ventilation frequency (fV) in response to hypoxia in adult fish depends on ionotropic N-methyl-D-aspartate (NMDA) receptors. Nonetheless, the ontogeny of central control mechanisms mediating hypoxic ventilatory chemoreflexes in lower vertebrates has not been studied. Therefore, the aim of this study was to determine when the hypoxic ventilatory response during zebrafish (Danio rerio) development is mediated via NMDA receptors, by performing physiological experiments and western blot analysis of NMDA receptor subunits. Zebrafish larvae at stages 4-16 days post-fertilisation (dpf) were exposed to an hypoxic pulse in control groups and in groups treated with MK801 (NMDA receptor antagonist). The hypoxic increase in fV was present at all larval stages, and it matured during development. The reflex became MK801 sensitive at 8 dpf, but did not completely rely on a glutamatergic transmission until 13 dpf. This, together with changing subunit composition during the different stages (increasing amounts of NMDAR1 subunits and appearance of NMDAR2A subunits in adults), suggests that the amount of functional NMDA receptors needed to achieve a fully developed reflex is not attained until later stages. Furthermore, our results suggest that other non-NMDA receptor mechanisms are responsible for the hypoxia-induced increase in fV during the earlier developmental stages.

Animals↗

PubMed2006

Organisational factors, individual characteristics and social support: what determines the level of social support?

A large body of research has linked social support to health, but there are fewer studies that have focused on factors that influence the level of social support available and/or perceived by employees in different organisations. This cross-sectional study therefore investigated the relationship between on the one hand, organisational, individual and socio-demographic factors and on the other, the level of social support at the workplace, i.e., the degree of supervisor support and a supportive work atmosphere. Organisational variables (job demands, job control, job content), individual (self-esteem, mistrust) and socio-demographic variables (type of employer, occupational position, age, gender and educational level) were used as independent variables in the analyses. The sample consisted of 16,144 individuals at a variety of different organisations in Sweden, who had responded to a questionnaire covering different psychosocial and psychological stress factors ("the Stress Profile"). Multiple hierarchical regression analyses were performed separately for each of the two dependent variables, which yielded almost identical results, and indicated that organisational determinants, particularly perceived job control, had the largest impact on the degree of social support.

Adult↗

PubMed2003

Identification of central mechanisms vital for breathing in the channel catfish, Ictalurus punctatus.

To investigate central respiratory control mechanisms in channel catfish, microinjections of kainic acid (causing chemical lesion of neurons) or kynurenic acid (an antagonist of N-methyl-D-aspartate (NMDA), kainate and alpha-amino-3-OH-5-methyl-4-isooxazole-propionic-acid (AMPA) receptors) were made into the general visceral nucleus (nGV) of the medulla in anaesthetised spontaneously breathing animals. Kainic acid abolished the ventilatory movements, indicating that neurons in the nGV are crucial for maintaining normal breathing. Kynurenic acid did not affect normal breathing, but abolished the ventilatory responses to hypoxia, showing that ionotropic glutamate receptors in the nGV are vital for the production of oxygen chemoreceptor activated respiratory reflexes. In addition, immunohistochemistry of brain slices showed that interneurons and nerve fibres in the nGV display NMDA-immunoreactivity, which corroborates the physiological experiments. The results of this study suggest that neurons and glutamatergic pathways in the nGV are essential for ventilatory functions and hypoxic reflexes in channel catfish.

Animals↗

PubMed2003

Evidence for glutamatergic mechanisms in the vagal sensory pathway initiating cardiorespiratory reflexes in the shorthorn sculpin Myoxocephalus scorpius.

Glutamate is a major neurotransmitter of chemoreceptor and baroreceptor afferent pathways in mammals and therefore plays a central role in the development of cardiorespiratory reflexes. In fish, the gills are the major sites of these receptors, and, consequently, the terminal field (sensory area) of their afferents (glossopharyngus and vagus) in the medulla must be an important site for the integration of chemoreceptor and baroreceptor signals. This investigation explored whether fish have glutamatergic mechanisms in the vagal sensory area (Xs) that could be involved in the generation of cardiorespiratory reflexes. The locations of the vagal sensory and motor (Xm) areas in the medulla were established by the orthograde and retrograde axonal transport of the neural tract tracer Fast Blue following its injection into the ganglion nodosum. Glutamate was then microinjected into identified sites within the Xs in an attempt to mimic chemoreceptor- and baroreceptor-induced reflexes commonly observed in fish. By necessity, the brain injections were performed on anaesthetised animals that were fixed by 'eye bars' in a recirculating water system. Blood pressure and heart rate were measured using an arterial cannula positioned in the afferent branchial artery of the 3rd gill arch, and ventilation was measured by impedance probes sutured onto the operculum. Unilateral injection of glutamate (40-100 nl, 10 mmol l(-1)) into the Xs caused marked cardiorespiratory changes. Injection (0.1-0.3 mm deep) in different rostrocaudal, medial-lateral positions induced a bradycardia, either increased or decreased blood pressure, ventilation frequency and amplitude and, sometimes, an initial apnea. Often these responses occurred simultaneously in various different combinations but, occasionally, they appeared singly, suggesting specific projections into the Xs for each cardiorespiratory variable and local determination of the modality of the response. Response patterns related to chemoreceptor reflex activation were predominantly located rostral of obex, whereas patterns related to baroreceptor reflex activation were more caudal, around obex. The glutamate-induced bradycardia was N-methyl-D-aspartate (NMDA) receptor dependent and atropine sensitive. Taken together, our data provide evidence that glutamate is a putative player in the central integration of chemoreceptor and baroreceptor information in fish.

Afferent Pathways↗

PubMed2003

N-methyl-D-aspartate receptors mediate chemoreflexes in the shorthorn sculpin Myoxocephalus scorpius.

Glutamate microinjected into the vagal sensory area in the medulla produces cardiorespiratory responses mimicking oxygen chemoreflexes in fish. Here we directly investigate whether these reflexes are dependent on the ionotropic N-methyl-D-aspartate (NMDA) glutamate receptor. Fish were equipped with opercular, branchial and snout cannulae for measurements of cardiorespiratory parameters and drug injections. Oxygen chemoreceptor reflexes were evoked by rapid hypoxia, NaCN added into the blood (internal, 0.3 ml, 50 microg ml(-1)) and the mouth (external, 0.5 ml, 1 mg ml(-1)), before and after systemic administration of the NMDA receptor antagonist MK801 (3 mg kg(-1)). Hypoxia produced an MK801-sensitive increase in blood pressure and ventilation frequency, whereas the marked bradycardia and the increased ventilation amplitude were NMDA receptor-independent. The fish appeared more responsive to externally applied cyanide, but the injections and MK801 treatment did not distinguish whether external or internal oxygen receptors were differently involved in the hypoxic responses. In addition, using single-labelling immunohistochemistry on sections from the medulla and ganglion nodosum, the presence of glutamate and NMDA receptors in the vagal oxygen chemoreceptor pathway was established. In conclusion, these results suggest that NMDA receptors are putative central control mechanisms that process oxygen chemoreceptor information in fish.

Animals↗

PubMed2002

Cardiovascular effects of prostaglandin F(2 alpha) and prostaglandin E(2) in Atlantic cod (Gadus morhua).

Little is known of the cardiovascular functions of prostaglandins in non-mammalian vertebrates. There are indications that prostaglandins may have a function in haemostasis by constricting blood vessels in filament arteries in the fish gill after injury. Our aim was to examine the cardiovascular effect of the prostaglandins F(2 alpha) (PGF(2 alpha)) and E(2) (PGE(2)) with emphasis on branchial circulation. Intra-arterial injections of PGF(2 alpha) (10, 40, 160, 400 nmol kg(-1)) in cod caused a dose-dependent increase in ventral aortic blood pressure, a reduction in cardiac output, and an increase in gill vascular resistance. A contraction of filament arteries was observed with in vivo microscopy only seconds after injection. PGF(2 alpha) may therefore possibly be involved in a haemostatic vasoconstriction. In contrast, the most significant effects of PGE(2) appeared to be on the heart. PGE(2) also reduced dorsal aortic blood pressure.

Animals↗

PubMed2001

Pulmonary receptors in reptiles: discharge patterns of receptor populations in snakes versus turtles.

This study examines the effects of lung inflation/deflation with and without CO2 on the entire population of pulmonary receptors in the vagus nerve in two species of snakes and two species of turtles. We asked the question, "how does the response of the entire mixed population of pulmonary stretch receptors (PSR) and intrapulmonary chemoreceptors (IPC) in species possessing both differ from that in species with only PSR"? This was studied under conditions of artificial ventilation with the secondary goal of extending observations on the presence/absence of IPC to a further three species. Our results indirectly illustrate the presence of IPC in the Burmese python and South American rattlesnake but not the side necked turtle, adding support to the hypothesis that IPC first arose in diapsid reptiles. In both species of snake, CO2-sensitive discharge (presumably from IPC) predominated almost to the exclusion of CO2-insensitive discharge (presumably arising from PSR) while the opposite was true for both species of turtle. The data suggest that for animals breathing air under conditions of normal metabolism there is little to distinguish between the discharge profiles of the total population of receptors arising from the lungs in the different groups. Interestingly, however, under conditions of elevated environmental CO2 most volume-related feedback from the lungs is abolished in the two species of snakes, while under conditions of elevated metabolic CO2, it is estimated that volume feedback from the lungs would be enhanced in these same species.

Animals↗

PubMed2000

Branchial and circulatory responses to serotonin and rapid ambient water acidification in rainbow trout.

Although the branchial and cardiovascular effects of serotonin (5-hydroxytryptamine) have only partially been characterized, a physiological role for serotonin in the cardiorespiratory responses of fish to environmental changes such as reduced Ph has been suggested. Therefore, we have characterized and compared the effects of serotonin and a rapid reduction of Ph in the ambient water (from pH 8.8 to pH 4.0) on ventral and dorsal aortic blood pressures, heart rate, cardiac output, and arterial pH in rainbow trout, Onchorhynchus mykiss. In addition, the circulation in the branchial microvasculature was observed using in vivo epi-illumination microscopy. The fall in water Ph and injection of serotonin (100 nmol/kg) both increased the branchial resistance and reduced the efferent filamental artery (EFA) blood velocity. Nevertheless, quantitatively, the responses to the two stimuli were different. Although acid exposure caused a much more profound increase in branchial resistance compared with serotonin, the blood flow in the observable distal portion of the EFA was only reduced by 60% in acid water, while it stopped with serotonin. Regardless of the marked branchial resistance elevation, a constriction of the efferent filamental vasculature could not be seen during acid exposure, as occasionally was the case with serotonin. While methysergide completely abolished the serotonin-induced branchial events, it only modestly suppressed the acid-induced reduction of EFA blood velocity. In contrast, all of the systemic changes induced by serotonin and acidic water were insensitive to methysergide. In conclusion, acidic water and injected serotonin elevate the branchial resistance, but the involvement of a serotonergic component in the acidic response appears negligible.

Animals↗

PubMed2000

Cardiovascular and respiratory reflexes in the tropical fish, traira (Hoplias malabaricus): CO2/pH chemoresponses.

To examine the distribution and physiological role of CO2/pH-sensitive chemoreceptors in the gills of the tropical fish, traira (Hoplias malabaricus), fish were exposed to acute environmental hypercarbia (1.25, 2.5 and 5.0% CO2 in air) and subjected to injections of HCl into the ventral aorta and buccal cavity. This was done before and after selective denervation of branchial branches of the IXth and Xth cranial nerves to various gills arches. Hypercarbia produced a significant decrease in heart rate, a mild hypotension as well as increases in both ventilation rate and ventilation amplitude. The data suggest that the hypercarbic bradycardia and increase in ventilation frequency arise from receptors exclusively within the gills but present on more than the first gill arch, while extra-branchial receptors may also be involved in controlling the increase in ventilation amplitude. With the exception of a decrease in heart rate in response to HCl injected into the ventral aorta, the acid injections (internal and external) did not mimic the cardiorespiratory responses observed during hypercarbia suggesting that changes in CO2 are more important than changes in pH in producing cardiorespiratory responses. Finally, the data indicate that chemoreceptors sensitive to CO2/pH and to O2 in the gills of this species involved in producing ventilatory responses are distributed in a similar fashion, but that those involved in producing the bradycardia are not.

Animals↗

PubMed2000

Branchial receptors and cardiorespiratory reflexes in a neotropical fish, the tambaqui (Colossoma macropomum).

This study examined the location and physiological roles of branchial chemoreceptors involved in the cardiorespiratory responses to hypoxia and hypercarbia in a neotropical fish that exhibits aquatic surface respiration, the tambaqui (Colossoma macropomum). Fish were exposed to abrupt progressive environmental hypoxia (18. 6-1.3 kPa water P(O2)) and hypercarbia (water equilibrated with 5 % CO(2) in air, which lowered the water pH from 7.0 to 5.0). They were also subjected to injections of NaCN into the ventral aorta (to stimulate receptors monitoring the blood) and buccal cavity (to stimulate receptors monitoring the respiratory water). All tests were performed before and after selective denervation of branchial branches of cranial nerves IX and X to the gill arches. The data suggest that the O(2) receptors eliciting reflex bradycardia and increases in breathing frequency are situated on all gill arches and sense changes in both the blood and respiratory water and that the O(2) receptors triggering the elevation in systemic vascular resistance, breathing amplitude, swelling of the inferior lip and that induce aquatic surface respiration during hypoxia are extrabranchial, although branchial receptors also contribute to the latter two responses. Hypercarbia also produced bradycardia and increases in breathing frequency, as well as hypertension, and, while the data suggest that there may be receptors uniquely sensitive to changes in CO(2)/pH involved in cardiorespiratory control, this is based on quantitative rather than qualitative differences in receptor responses. These data reveal yet another novel combination for the distribution of cardiorespiratory chemoreceptors in fish from which teleologically satisfying trends have yet to emerge.

Animals↗

PubMed1999

Cardiovascular responses to adenosine in the antarctic fish pagothenia borchgrevinki

We have investigated the effects of adenosine on the cardiovascular system of the Antarctic fish Pagothenia borchgrevinki. Continuous measurements of ventral and dorsal aortic blood pressures, heart rate (fh) and ventral aortic blood flow (cardiac output, q_dot ) were made using standard cannulation techniques and a single-crystal Doppler flowmeter. On line measurements of arterial P(O2) were made using an oxygen electrode connected to an extracorporeal loop. Adenosine (10 nmol kg(-)(1)) and the specific A(1)-receptor agonist N(6)-cyclopentyladenosine (CPA) elicited biphasic changes in the branchial and systemic resistances. While there was an initial decrease in the branchial resistance followed by an increase, the opposite was true for the systemic response. The resistance changes were significantly attenuated by aminophylline (a P(1)-receptor antagonist) and 8-cyclopentyltheophylline (CPT; an A(1)-receptor antagonist). In addition, adenosine induced an aminophylline-sensitive decrease in the arterial P(O2). The reduction was attenuated when pre-injection arterial P(O2) was low. Adenosine and CPA also caused a marked reduction in fh, with CPA being more potent. The bradycardia was blocked by aminophylline and CPT, demonstrating an involvement of A(1) receptors in this response.

Journal Article↗

PubMed1999

Cardiovascular and gill microcirculatory effects of endothelin-1 in atlantic cod: evidence for pillar cell contraction

Endothelin-1 (ET-1) has been shown to cause a considerable increase in the vascular resistance of fish gills. In trout, recent evidence suggest that this is the result of pillar cell contraction in the gill lamellae. Using epi-illumination microscopy to observe the gill lamellae of anaesthetised Atlantic cod (Gadus morhua), we show that ET-1 (100 ng kg-1, injected into the ventral aorta) causes an increase in pillar cell diameter, consistent with pillar cell contraction, and a shift of intralamellar blood flow from the lamellar sheet to the outer marginal channels. Simultaneously, there was an increase in ventral aortic blood pressure, a reduction in cardiac output, an increase in gill vascular resistance and a reduction in the oxygen partial pressure of venous blood. All these effects were blocked by the ETA/ETB receptor antagonist bosentan (5 mg kg-1). Pillar cell contraction is likely to be a mechanism for matching the functional respiratory surface area with the instantaneous respiratory needs of the fish.

Journal Article↗

PubMed1998

Gill blood flow control.

The arrangement of the fish gill vasculature is quite complex, and varies between the different fish groups. The use of vascular casting techniques has greatly enhanced our knowledge of the anatomy of the branchial microcirculation, not least through the contributions of Pierre Laurent and co-workers at Strasbourg. At different physiological situations, the contact surface between water and blood (functional surface area) varies to balance oxygen uptake against osmotic water flow ("respiratory-osmoregulatory compromise"). This is controlled by nerves and by blood-borne or locally released substances that affect blood flow patterns in the gill. Histochemical techniques have been used to demonstrate neurotransmitter substances in the branchial innervation. In combination with physioly-osmoregulatory compromise" at different physiological situations.

Animals↗

PubMed1998

Acute defense mechanisms against hemorrhage from mechanical gill injury in rainbow trout.

By cutting gill filaments in anesthetized rainbow trout (Oncorhynchus mykiss), observing the bleeding through a stereomicroscope, and using blockers of various known endogenous filament artery vasoconstrictors, we have here attempted to characterize hemostatic mechanisms in gills. The immediate hemostatic response to a cut in a gill filament artery was a local vasoconstriction, stopping the hemorrhage within approximately 20 s. In heparinized fish, the hemorrhage recommenced after approximately 8 min, suggesting that the vasoconstriction soon subsides and blood clotting becomes responsible for the hemostasis. Antagonists of acetylcholine, adenosine, and serotonin receptors were unable to block the hemostatic vasoconstriction. Also, tetrodotoxin was without effect, indicating a nonnervous origin. By contrast, indomethacin significantly affected the measured bleeding times, suggesting that eicosanoids play a significant role in this process (possibly by stimulating vasoconstriction and/or by inducing local thrombocyte aggregation). By possessing several hundred virtually identical filaments with readily observable vasculature, the fish gill appears to be a good experimental model for studying hemostatic mechanisms.

Animals↗

PubMed1998

A role of 5-HT2 receptors in the gill vasculature of the antarctic fish Pagothenia borchgrevinki.

This study was conducted to describe the cardiovascular responses to intra-arterial injections of serotonin in the Antarctic fish Pagothenia borchgrevinki and to elucidate the underlying mechanisms. Immunohistochemistry was used to localise serotonin-containing cells within the gills. Simultaneous and continuous recordings of ventral and dorsal aortic blood pressure, heart rate and ventral aortic blood flow (cardiac output) were made using standard cannulation procedures in combination with Doppler flow measurement. An extracorporeal loop with an in-line oxygen electrode allowed continuous measurements of arterial oxygen pressure PaO2. Pre-branchial injection of serotonin (5-hydroxytryptamine, 5-HT) or the 5-HT2 receptor agonist alpha-methylserotonin increased the branchial vascular resistance and ventral aortic pressure, while the 5-HT1 receptor agonist piperazine was without effect. The branchial vasoconstriction produced by serotonin injection was completely blocked by the 5-HT1/5-HT2 receptor antagonist methysergide and the branchial vasoconstriction produced by WIDTH="9" HEIGHT="12" ALIGN="BOTTOM" NATURALSIZEFLAG= alpha-methylserotonin injection was completely blocked by the specific 5-HT2 receptor antagonist LY53857. The results suggest that the 5-HT2 receptor alone mediates the branchial vasoconstriction. Serotonin also mediated a methysergide-sensitive reduction in PaO2, the reduction being greatest when the pre-injection PaO2 value was high. 5-HT-immunoreactive cells and nerve fibres were present within the gill tissues. All the 5-HT-immunoreactive cells were located on the efferent side of the filaments, but 5-HT-immunoreactive nerve fibres were found lining both of the branchial arteries. Our findings demonstrate a potential serotonergic control system for the gills in Pagothenia borchgrevinki. In contrast to its effects on the branchial vasculature, serotonin produced a methysergide-insensitive decrease in the systemic vascular resistance. However, neither the specific 5-HT1 nor 5-HT2 receptor agonists produced a decrease in the resistance of the systemic vasculature. The nature of the serotonergic receptor(s) inducing vasodilation in teleost fish is uncertain.

Animals↗

PubMed1997

Neurochemical mechanisms behind gill microcirculatory responses to hypoxia in trout: in vivo microscopy study.

In vivo microscopy combined with systemic blood flow and pressure measurements were used to examine the hemodynamic and microcirculatory responses to hypoxia in gills of rainbow trout and to clarify if the underlying mechanisms are adrenergic, cholinergic, serotonergic, or adenosinergic. Hypoxia (P(O2) 1.07-1.33 kPa) reduced, halted, or reversed the blood flow in the distal portion of the efferent filamental artery (EFA). Simultaneously, a large overflow to the central venous system appeared, allowing a continuous flow through many of the secondary lamellae. No vasoconstriction could be observed in this portion of the filament, showing that a vasoconstriction occurred elsewhere, possibly at the EFA sphincter, because the gill resistance (R(G)) increased. These effects were mimicked by prebranchial injection of acetylcholine, a treatment that also strongly constricted the distal efferent filamental vasculature. Atropine blocked most of the hypoxia-induced hemodynamic changes, although a minor increase in R(G) remained. The latter appeared to be of a nonadrenergic noncholinergic origin, being unaffected by additional treatment with an alpha-adrenoreceptor antagonist. It was also unaffected by blockers of serotonin and adenosine-A1 receptors. Other responses seen included a cholinergic maintenance of the systemic resistance during hypoxia and an alpha-adrenoceptor-mediated posthypoxic hypertension. This study demonstrates that hypoxia evoked a cholinergic reflex vasoconstriction located at proximal parts of the efferent filamental vasculature.

Acetylcholine↗

PubMed1996

Branchial and systemic roles of adenosine receptors in rainbow trout: an in vivo microscopy study.

The purinergic branchial vasomotor control in rainbow trout (Oncorhynchus mykiss) was studied using an epi-illumination microscope equipped with a water-immersion objective. Cardiac output (Q), heart rate, and dorsal (PDA) and ventral (PVA) aortic pressures were recorded simultaneously. Prebranchial injection of adenosine or the A1-receptor agonist N6-cyclopentyl-adenosine (CPA) constricted the distal portion of the filament vasculature, which coincided with an increase of PVA. The A2-receptor agonist PD-125944 was without effect. After adenosine and CPA injection, an overflow of blood to the secondary system was repeatedly observed unless blood flow came to a complete stop. The lack of a concomitant reduction of Q suggested a redistribution of blood to the secondary system and to more proximal parts of the filament. The branchial effects of adenosine and CPA were completely blocked by the unspecific adenosine receptor antagonist amino-phylline and the specific A1-receptor antagonist N6-cyclopen-tyltheophylline. The results suggest that A1-receptors alone mediate the branchial vasoconstriction observed. Thus the responses of the branchial vasculature to adenosine include a vasoconstriction of the filament vasculature mediated via specific A1 receptors and a redistribution of blood flow to the secondary system and to proximal parts of the filament. Additional cardiovascular effects of adenosine included decreased systemic vascular resistance and heart rate.

Adenosine↗

PubMed1995

Control of gill filament blood flow by serotonin in the rainbow trout, Oncorhynchus mykiss.

The effects of exogenously applied serotonin [5-hydroxytryptamine (5-HT)] on the distal arterial vasculature of gill filaments were observed using an epi-illumination microscope equipped with a water-immersion objective and connected to a video camera. In addition, ventral aortic flow (Q) and celiac artery pressure (PCA) were measured. Intra-arterial injection of serotonin (100 nmol/kg) completely stopped the blood flow in the distal part of the filaments and caused a rapid decrease of PCA. Repeatedly, the flow reduction was found to coincide with a constriction of the distal portion of the efferent filamental vasculature. Because there was no concomitant reduction in Q, it is concluded that a redistribution of blood to more proximal parts of the filaments occurred. After treatment with the serotonergic receptor antagonist methysergide, the vasoconstrictor effect of serotonin on the filamental vasculature was eliminated, while a decrease in PCA was still observed. The results demonstrate a specific site(s) for the serotonergic vasoconstriction in the distal portion of the filament.

Animals↗