Long-term effects on cardiorespiratory and behavioral responses in male and female rats prenatally exposed to cannabinoid.

Development of the respiratory system can be affected by the use of drugs during pregnancy, as the prenatal phase is highly sensitive to pharmacological interventions, resulting in long-term consequences. The deleterious effects of external cannabinoids during gestation may be related to negative interference in central nervous system formation, cardiorespiratory system function, and behavioral disorders. Nevertheless, the impact of external cannabinoids on cardiorespiratory network development, chemosensitivity, and its future consequences in adulthood is still unclear. We evaluated the effects of prenatal exposure to a synthetic cannabinoid (WIN 55,212-2, 0.5 mg.kg-1.day-1) on the cardiorespiratory control and panic-like behavior of male and female rats in adulthood. Exogenous cannabinoid exposure during pregnancy resulted in a sex-dependent difference in breathing control. Specifically, males showed increased chemosensitivity to CO2 and O2, while females exhibited decreased sensitivity. Altered cardiovascular control was evident, with prenatally treated males and females being more susceptible to hypertension and tachycardia under adverse environmental conditions. Moreover, WIN-treated males exhibited higher fragmentation of sleep episodes, while females displayed anxiolytic and panicolytic behavioral responses to CO2. However, no changes were observed in the mechanical component of the respiratory system, and there were no neuroanatomical alterations, such as changes in the expression of CB1 receptors in the brainstem or in the quantification of catecholaminergic and serotonergic neurons. These findings highlight that external interference in cannabinoid signaling during fetal development causes sex-specific long-lasting effects for the cardiorespiratory system and behavioral responses in adulthood.

The influence of the post-hepatic septum and abdominal volume on breathing mechanics in the lizard Salvator merianae (Squamata: Teiidae).

Teiid lizards possess an incomplete post-hepatic septum (PHS) separating the lungs and liver from the remaining viscera, and within this group, Salvator merianae has the most complete PHS. In this study, we explored the combined effects of the presence of the PHS and alterations in abdominal volume on the mechanics of the respiratory system. The PHS is believed to act as a mechanical barrier, mitigating the impact of the viscera on the lungs. Using established protocols, we determined static (Cstat) and dynamic (Cdyn) compliance, lung volume and work of breathing for the respiratory system in tegu lizards with intact (PHS+) or removed (PHS-) PHS, combined with (balloon+) or without (balloon-) increased abdominal volume. The removal of the PHS significantly reduced resting lung volume and Cdyn, as well as significantly increasing the work of breathing. An increase in abdominal volume significantly reduced Cstat, Cdyn, and resting and maximum lung volume. However, the work of breathing increased less in the PHS+/balloon+ treatment than in the PHS- treatments. These results highlight the barrier function of the PHS within the tegu lizard's body cavity. The septum effectively reduces the impact of the viscera on the respiratory system, enabling the lungs to be ventilated at a low work level, even when abdominal volume is increased. The presence of the PHS in teiid lizards underscores how extrapulmonary structures, such as septal divisions of the body cavity, can profoundly affect pulmonary breathing mechanics.

Surface tension in biological systems - a common problem with a variety of solutions.

Water is of fundamental importance to living organisms, not only as a universal solvent to maintain metabolic activity but also due to the effects the physical properties of water have on different organismal structures. In this review, we explore some examples of how living organisms deal with surfaces covered with or in contact with water. While we do not intend to describe all possible forms of interactions in every minute detail, we would like to draw attention to this intriguing interdisciplinary subject and discuss the positive and negative effects of the interaction forces between water molecules and organisms. Topics explored include locomotion on water, wettability of surfaces, benefits of retaining a film of air while submerged (Salvinia effect), surface tension of water inhibiting air-breathing, accumulation of water in small tubes, surface tension in non-mammalian and mammalian respiratory systems. In each topic, we address the importance of interactions with water and the adaptations seen in an organism to solve the surface-related challenges, trying to explore the different selective pressures acting onto different organisms allowing exploring or compensating these surface-related interactions.

Modeling of the respiratory system of the long-necked Triassic reptile Tanystropheus (Archosauromorpha).

All known species of the Triassic archosauromorph genus Tanystropheus are known to have had the longest neck in proportion to their torso. This feature is related to a series of ventilatory challenges since an increase in neck length also increases airway length and, therefore, the volume of stagnant air that does not reach the lungs, the dead space volume. Based on this challenge, the objective of the present study was to model the type of respiratory system of Tanystropheus able to meet its metabolic demands during the early Triassic period. The modeling was based on allometric relations for morphological and physiological ventilatory and metabolic variables, and to do so, the mean body mass of Tanystropheus was estimated based on three different methods. In addition, the tracheal airflow was also estimated based on the proportions of Tanystropheus elongated neck, the results of allometric modeling, and fundamental equations of fluid mechanics. The estimation of the body mass indicated that an animal of 3.6 m would possess a body mass of 50.6 ± 21.6 kg. Allometric modeling suggested that the respiratory system best suited to Tanystropheus' oxygen demands, especially during activity, would be a generic reptilian-like respiratory system composed of multicameral lungs. The best respiratory pattern to maintain adequate tracheal flow rates and effective pulmonary ventilation would be one ventilating the relatively narrower trachea at lower frequencies to deal with tracheal dead space volume.

Patterns of energetic substrate modifications in response to feeding in boas, Boa constrictor (Serpentes, Boidae).

Ambush-foraging snakes that ingest large meals might undergo several months without eating when they use the internal reserves to support the energetic costs of living. Then, morphological and physiological processes might be orchestrated during the transition from fasting to the postprandial period to rapidly use the energetic stores while the metabolic rate is elevated in response to food intake. To understand the patterns of substrates deposition after feeding, we accessed the morphological and biochemical response in Boa constrictor snakes after two months of fasting and six days after feeding. We followed the plasma levels of glucose, total proteins, and total lipids, and we performed the stereological ultrastructural analysis of the liver and the proximal region of the intestine to quantify glycogen granules and lipid droplets. In the same tissues and stomach, we measured the activity of the enzyme fructose-1,6-biphosphatase (FBPase1) involved in the gluconeogenic pathway, and we measured pyruvate kinase (PK) and lactate dehydrogenase (LDH) enzymatic activities involved in the anaerobic pathway in the liver. Briefly, our results indicated an increase in boas' plasma glucose one day after meal intake compared to unfed snakes. The hepatic glycogen reserves were continuously restored within days after feeding. Also, the enzymes involved in the energetic pathways increased activity six days after feeding in the liver. These findings suggest a quick restoring pattern of energetic stores during the postprandial period.

The influence of the post-pulmonary septum and submersion on the pulmonary mechanics of Trachemys scripta (Cryptodira: Emydidae).

The respiratory system of chelonians needs to function within a mostly solid carapace, with ventilation depending on movements of the flanks. When submerged, inspiration has to work against hydrostatic pressure. We examined breathing mechanics in Trachemys scripta while underwater. Additionally, as the respiratory system of T. scripta possesses a well-developed post-pulmonary septum (PPS), we investigated its role by analyzing the breathing mechanics of lungs with and without their PPS attached. Static compliance was significantly increased in submerged animals and in animals with and without their PPS, while removal of the PPS did not result in a significantly different static compliance. Dynamic compliance was significantly affected by changes in volume and frequency in every treatment, with submergence significantly decreasing dynamic compliance. The presence of the PPS significantly increased dynamic compliance. Submersion did not significantly alter work per ventilation, but caused minute work of breathing to be much greater at any frequency and ventilation level analyzed. Lungs with or without their PPS did not show significantly different work per ventilation when compared with the intact animal. Our results demonstrate that submersion results in significantly altered breathing mechanics, increasing minute work of breathing greatly. The PPS was shown to maintain a constant volume within the animal's body cavity, wherein the lungs can be ventilated more easily, highlighting the importance of this coelomic subdivision in the chelonian body cavity.

Allometric relations of respiratory variables in Amniota: Effects of phylogeny, form, and function.

Biological variables are frequently described by analyzing scaling relationships of the variable against body mass (MB). Respiratory variables are no exception and allometric relations for oxygen consumption, pulmonary ventilation, tidal volume, breathing frequency, and lung volume have been described in the literature. While the allometric relations of respiratory variables given for mammals and birds are very consistent among different studies, scaling relationships for non-avian reptiles have only been scarcely described and show considerable variation between studies. Since no comprehensive study of allometric relations of respiratory variables has been carried out comparing the different groups of non-avian reptiles, we analyzed morphological and physiological variables of the respiratory system of crocodilians, chelonians, lizards, snakes, birds, and mammals, regarding the allometric relations of each variable from a phylogenetic perspective as well as related to lung morphology. Our results indicated that few respiratory variables possess significant phylogenetic signals and that tidal volume, breathing frequency (except mammals), and air convection requirement were independent of phylogeny. Contrary to the literature, lung volume of amniotes scaled isometrically to MB, with the exception of lizards (MB0.78). Air convection requirement scaled isometrically in mammals and birds, but was more variable among non-avian reptiles, from a taxonomic perspective and in regard to different lung structures. In conclusion, respiratory variables among non-avian reptiles scaled more variably than previously expected, both according to phylogeny and to lung type, warranting future studies to explore structure-function relations of the reptilian respiratory system, especially regarding snakes and crocodilians, since these groups had very few data available for analysis.

Parabronchial remodeling in chicks in response to embryonic hypoxia.

The embryonic development of parabronchi occurs mainly during the second half of incubation in precocious birds, which makes this phase sensitive to possible morphological modifications induced by O2 supply limitation. Thus, we hypothesized that hypoxia during the embryonic phase of parabronchial development induces morphological changes that remain after hatching. To test this hypothesis, chicken embryos were incubated entirely (21 days) under normoxia or partially under hypoxia (15% O2 during days 12 to 18). Lung structures, including air capillaries, blood capillaries, infundibula, atria, parabronchial lumen, bronchi, blood vessels larger than capillaries and interparabronchial tissue, in 1- and 10-day-old chicks were analyzed using light microscopy-assisted stereology. Tissue barrier and surface area of air capillaries were measured using electron microscopy-assisted stereology, allowing for calculation of the anatomical diffusion factor. Hypoxia increased the relative volumes of air and blood capillaries, structures directly involved in gas exchange, but decreased the relative volumes of atria in both groups of chicks, and the parabronchial lumen in older chicks. Accordingly, the surface area of the air capillaries and the anatomical diffusion factor were increased under hypoxic incubation. Treatment did not alter total lung volume, relative volumes of infundibula, bronchi, blood vessels larger than capillaries, interparabronchial tissue or the tissue barrier of any group. We conclude that hypoxia during the embryonic phase of parabronchial development leads to a morphological remodeling, characterized by increased volume density and respiratory surface area of structures involved in gas exchange at the expense of structures responsible for air conduction in chicks up to 10 days old.

The respiratory mechanics of the yacare caiman (Caiman yacare).

The structure and function of crocodilian lungs are unique compared with those of other reptiles. We examined the extent to which this and the semi-aquatic lifestyle of crocodilians affect their respiratory mechanics. We measured changes in intratracheal pressure in adult and juvenile caiman (Caiman yacare) during static and dynamic lung volume changes. The respiratory mechanics of juvenile caiman were additionally measured while the animals were floating in water and submerged at 30, 60 and 90 deg to the water's surface. The static compliance of the juvenile pulmonary system (2.89±0.22 ml cmH2O-1 100 g-1) was greater than that of adults (1.2±0.41 ml cmH2O-1 100 g-1), suggesting that the system stiffens as the body wall becomes more muscular and keratinized in adults. For both age groups, the lungs were much more compliant than the body wall, offering little resistance to air flow (15.35 and 4.25 ml cmH2O-1 100 g-1 for lungs, versus 3.39 and 1.67 ml cmH2O-1 100 g-1 for body wall, in juveniles and adults, respectively). Whole-system dynamic mechanics decreased with increasing ventilation frequency (fR), but was unaffected by changes in tidal volume (VT). The vast majority of the work of breathing was required to overcome elastic forces; however, work to overcome resistive forces increased proportionally with fR Work of breathing was higher in juvenile caiman submerged in water at 90 deg because of an increase in work to overcome both elastic and flow resistive forces. The lowest power of breathing was found to occur at high fR and low VT for any given minute ventilation (V̇E) in caiman of all ages.

Buccal jet streaming and dead space determination in the South American lungfish, Lepidosiren paradoxa.

The "jet stream" model predicts an expired flow within the dorsal part of the buccal cavity with small air mixing during buccal pump ventilation, and has been suggested for some anuran amphibians but no other species of air breathing animal using a buccal force pump has been investigated. The presence of a two-stroke buccal pump in lungfish, i.e. expiration followed by inspiration, was described previously, but no quantitative data are available for the dead-space of their respiratory system and neither a detailed description of airflow throughout a breathing cycle. The present study aimed to assess the degree of mixing of fresh air and expired gas during the breathing cycle of Lepidosiren paradoxa and to verify the possible presence of a jet stream during expiration in this species. To do so, simultaneous measurements of buccal pressure and ventilatory airflows were carried out. Buccal and lung gases (PCO2 and PO2) were also measured. The effective ventilation was calculated and the dead space estimated using Bohr equations. The results confirmed that the two-stroke buccal pump is present in lungfish, as it is in anuran amphibians. The present approaches were coherent with a small dead space, with a very small buccal-lung PCO2 difference. In the South American lungfish the dead space (VD) as a percentage of tidal volume (VT) (VD / VT) ranged from 4.1 to 12.5%. Our data support the presence of a jet stream and indicate a small degree of air mixing in the buccal cavity. Comparisons with the literature indicate that these data are similar to previous data reported for the toad Rhinella schneideri.

Seasonal variation of hypoxic and hypercarbic ventilatory responses in the lizard Tropidurus torquatus.

Carbon dioxide (CO2) and oxygen (O2) influence the breathing pattern of reptiles, especially when CO2 is in excess or O2 at low concentrations and the effects of these gases on the respiratory response varies according to the species. In addition to respiratory gases, seasonal changes can also modulate breathing pattern and ventilatory responses to hypoxia and hypercarbia. Therefore, the present study investigated the breathing pattern and ventilatory responses to hypercarbia (5% CO2) and hypoxia (5% O2) of the Neotropical lizard Tropidurus torquatus over a period of one year, covering all seasons (summer, autumn, winter and spring). Our data suggest that like other ectothermic sauropsids, Tropidurus torquatus possesses distinct ventilatory responses to hypoxia and hypercarbia, being more sensitive to changes in CO2 than in O2. Additionally, the ventilatory responses to hypoxia were more pronounced during summer and hypercanic and pos-hypercapnic ventilatory response was reduced during spring, suggesting that seasonality modulates the control of ventilation in this species.

Effects of aerial hypoxia and temperature on pulmonary breathing pattern and gas exchange in the South American lungfish, Lepidosiren paradoxa.

The South American lungfish Lepidosiren paradoxa is an obligatory air-breathing fish possessing well-developed bilateral lungs, and undergoing seasonal changes in its habitat, including temperature changes. In the present study we aimed to evaluate gas exchange and pulmonary breathing pattern in L. paradoxa at different temperatures (25 and 30°C) and different inspired O2 levels (21, 12, 10, and 7%). Normoxic breathing pattern consisted of isolated ventilatory cycles composed of an expiration followed by 2.4±0.2 buccal inspirations. Both expiratory and inspiratory tidal volumes reached a maximum of about 35mlkg-1, indicating that L. paradoxa is able to exchange nearly all of its lung air in a single ventilatory cycle. At both temperatures, hypoxia caused a significant increase in pulmonary ventilation (V̇E), mainly due to an increase in respiratory frequency. Durations of the ventilatory cycle and expiratory and inspiratory tidal volumes were not significantly affected by hypoxia. Expiratory time (but not inspiratory) was significantly shorter at 30°C and at all O2 levels. While a small change in oxygen consumption (V̇O2) could be noticed, the carbon dioxide release (V̇CO2, P=0.0003) and air convection requirement (V̇E/V̇O2, P=0.0001) were significantly affected by hypoxia (7% O2) at both temperatures, when compared to normoxia, and pulmonary diffusion capacity increased about four-fold due to hypoxic exposure. These data highlight important features of the respiratory system of L. paradoxa, capable of matching O2 demand and supply under different environmental change, as well as help to understand the evolution of air breathing in lungfish.

Recovery of pulmonary structure and exercise capacity by treatment with granulocyte-colony stimulating factor (G-CSF) in a mouse model of emphysema.

Emphysema is a chronic obstructive pulmonary disease characterized abnormal dilatation of alveolar spaces, which impairs alveolar gas exchange, compromising the physical capacity of a patient due to airflow limitations. Here we tested the effects of G-CSF administration in pulmonary tissue and exercise capacity in emphysematous mice. C57Bl/6 female mice were treated with elastase intratracheally to induce emphysema. Their exercise capacities were evaluated in a treadmill. Lung histological sections were prepared to evaluate mean linear intercept measurement. Emphysematous mice were treated with G-CSF (3 cycles of 200 µg/kg/day for 5 consecutive days, with 7-day intervals) or saline and submitted to a third evaluation 8 weeks after treatment. Values of run distance and linear intercept measurement were expressed as mean ± SD and compared applying a paired t-test. Effects of treatment on these parameters were analyzed applying a Repeated Measures ANOVA, followed by Tukey's post hoc analysis. p < 0.05 was considered statistically significant. Twenty eight days later, animals ran significantly less in a treadmill compared to normal mice (549.7 ± 181.2 m and 821.7 ± 131.3 m, respectively; p < 0.01). Treatment with G-CSF significantly increased the exercise capacity of emphysematous mice (719.6 ± 200.5 m), whereas saline treatment had no effect on distance run (595.8 ± 178.5 m). The PCR cytokines genes analysis did not detect difference between experimental groups. Morphometric analyses in the lung showed that saline-treated mice had a mean linear intercept significantly higher (p < 0.01) when compared to mice treated with G-CSF, which did not significantly differ from that of normal mice. Treatment with G-CSF promoted the recovery of exercise capacity and regeneration of alveolar structural alterations in emphysematous mice.

Air-breathing behavior and physiological responses to hypoxia and air exposure in the air-breathing loricariid fish, Pterygoplichthys anisitsi.

Hypoxic water and episodic air exposure are potentially life-threatening conditions that fish in tropical regions can face during the dry season. This study investigated the air-breathing behavior, oxygen consumption, and respiratory responses of the air-breathing (AB) armored catfish Pterygoplichthys anisitsi. The hematological parameters and oxygen-binding characteristics of whole blood and stripped hemoglobin and the intermediate metabolism of selected tissue in normoxia, different hypoxic conditions, and after air exposure were also examined. In normoxia, this species exhibited high activity at night and AB behavior (2-5 AB h(-1)). The exposure to acute severe hypoxia elicited the AB behavior (4 AB h(-1)) during the day. Under progressive hypoxia without access to the water surface, the fish were oxyregulators with a critical O2 tension, calculated as the inspired water O2 pressure, as 47 ± 2 mmHg. At water O2 tensions lower than 40 mmHg, the fish exhibited continuous apnea behavior. The blood exhibited high capacity for transporting O2, having a cathodic hemoglobin component with a high Hb-O2 affinity. Under severe hypoxia, the fish used anaerobic metabolism to maintain metabolic rate. Air exposure revealed physiological and biochemical traits similar to those observed under normoxic conditions.

Effects of water restriction and dirt on grooming behavior in neotropical rodents (Trinomys setosus and T. yonenagae) (Echimyidae).

Grooming in rodents presents an evolutionarily conserved behavioral pattern that may cause water loss since saliva is deposited during washing onto large body surfaces. Trinomys yonenagae and Trinomys setosus are sister species of spiny rats occurring in Brazil, the former inhabiting a paleodesert of fixed dunes in the Caatinga, the latter being found in mesic environments of the Atlantic Forest. Consequently, it is expected that both species evolved under different selective pressures related to water balance, with T. yonenagae presenting mechanisms for dealing with water deprivation not found in T. setosus. Reduction of self-cleaning expression seems to offer a possible way to save water, as previously suggested by studies of the sand-dwelling spiny rat. Therefore, we propose to investigate grooming under four conditions: 'control' (C), a regimen of 'water restriction' (WR), of 'dirt' (D), and the combination of both conflicting stimuli (WR + D), in T. setosus, T. yonenagae, and Rattus norvegicus to compare the behavioral responses of these species. The main differences are observed in the forest dweller: T. setosus expresses a low relative duration of face washing under C, whose value is intermediate between the ones found in the two other species. WR treatment does not alter this pattern, however, the addition of dirt (D, WR + D) significantly increases the relative duration of washing in relation to C. Locomotor activity is decreased both in T. setosus and Wistar rats when they are under WR, a situation that could jeopardize antipredatory performance. T. yonenagae, the sand dweller, maintains a significantly lower expression of washing under C, as previously suggested, and under WR, D and WR + D. In addition, differently from the other two species the sand dweller maintains a normal activity level during all treatments. This study suggests differences in grooming as a strategy alluding to water balance by the two spiny rats inhabiting different ecosystems. A significantly clear pattern that saves water is observed in T. yonenagae, which probably has contributed to his evolution in one of the hottest semiarid areas of the world.

Morphological and physiological traits of the respiratory system in Iguana iguana and other non-avian reptiles.

Functional morphology considers form and function to be intrinsically related. To understand organismal functions, a detailed knowledge of morphological and physiological traits is necessary. Regarding the respiratory system, the combined knowledge about pulmonary morphology and respiratory physiology is fundamental to understand how animals exchange gases and regulate critical functions to sustain metabolic activity. In the present study, the paucicameral lungs of Iguana iguana were analyzed morphometrically through stereological analysis using light and transmission electron images and compared with unicameral and multicameral lungs of six other non-avian reptiles. The morphological data were combined with physiological information to perform a principal component analysis (PCA) and phylogenetic tests of the relationship of the respiratory system. Iguana iguana, Lacerta viridis, and Salvator merianae presented similar pulmonary morphologies and physiologies when compared to Varanus examthematicus, Gekko gecko, Trachemys scripta, and Crocodylus niloticus. The former species showed an elevated respiratory surface area (%AR), a high diffusion capacity, a low volume of total parenchyma (VP), a low percentage of parenchyma concerning the lung volume (VL), and a higher surface/volume ratio of the parenchyma (SAR/VP), with high respiratory frequency (fR) and consequently total ventilation. The total parenchymal surface area (SA), effective parenchymal surface-to-volume ratio (SAR/VP), respiratory surface area (SAR), and anatomical diffusion factor (ADF) showed a phylogenetic signal, evidence that the morphological traits are more strongly correlated with the species' phylogeny than the physiological traits. In sum, our results indicated that the pulmonary morphology is intrinsically related to physiological traits of the respiratory system. Furthermore, phylogenetic signal tests also indicate that morphological traits are more likely to be evolutionary conserved than physiological traits, suggesting that evolutive physiological adaptations in the respiratory system could happen faster than morphological changes.

Temperature effects on oxygen consumption and breathing pattern in juvenile and adult Chelonoidis carbonarius (Spix, 1824).

The effects of temperature on breathing pattern and oxygen consumption are being investigated in juvenile tortoises and compared to adults, in order to understand physiological adjustments of the respiratory system as related to body size, especially regarding the energetic expenditure associated with growth. We analyzed the breathing pattern and oxygen consumption of juvenile and adult red-footed tortoises (Chelonoidis carbonarius, Cryptodira: Testudinidae). The animals (N = 9; body mass ranging from 0.03 Kg to 2.5 Kg) were exposed to normoxic-normocarbic conditions using open respirometry in order to determine the breathing pattern and oxygen consumption in three different temperatures (15, 25, 35 °C). The obtained results showed intermittent breathing pattern in all tested temperatures in juveniles and adults. Tidal volume was not affected by changes in temperature, while breathing frequency increased significantly with increasing temperature, leading to a significant increment in minute ventilation between 15 and 35 °C. Mass specific oxygen consumption increased significantly with temperature and juveniles showed greater values when compared to adults. The alterations in the ventilatory response to temperature changes occurred in order to maintain the oxygen supply with increased metabolic activity. The differences between juveniles and adults in breathing frequency lead to juveniles needing a lower ventilation rate to perform gas exchange while extracting more oxygen. While these differences might be attributed to a greater metabolic expenditure during development, scaling effects on respiratory variables might be the main contributors to the found differences.

Sex- and age-specific respiratory alterations induced by prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 in rats.

BACKGROUND AND PURPOSE: Cannabis legalization has risen in many countries, and its use during pregnancy has increased. The endocannabinoid system is present in the CNS at early stages of embryonic development, and regulates functional brain maturation including areas responsible for respiratory control, data on the influence of external cannabinoids on the development of the respiratory system and possible consequences during postnatal life are limited. EXPERIMENTAL APPROACH: We evaluated the effects of prenatal exposure to synthetic cannabinoid (WIN 55,212-2 [WIN], 0.5 mg·kg-1 ·day-1 ) on the respiratory control system in neonatal (P0, P6-7 and P12-13) and juvenile (P27-28) male and female rats. KEY RESULTS: WIN administration to pregnant rats interfered sex-specifically with breathing regulation of offspring, promoting a greater sensitivity to CO2 at all ages in males (except P6-7) and in juvenile females. An altered hypoxic chemoreflex was observed in P0 (hyperventilation) and P6-7 (hypoventilation) males, which was absent in females. Along with breathing alterations, brainstem analysis showed an increase in the number of catecholaminergic neurons and cannabinoid receptor type 1 (CB1 ) and changes in tissue respiration in the early males. A reduction in pulmonary compliance was observed in juvenile male rats. Preexposure to WIN enhanced spontaneous apnoea and reduced the number of serotoninergic (5-HT) neurons in the raphe magnus nucleus of P0 females. CONCLUSIONS AND IMPLICATIONS: These data demonstrate that excess stimulation of the endocannabinoid system during gestation has prolonged and sex-specific consequences for the respiratory control system.

Effects of different levels of hypoxia and hypercarbia on ventilation and gas exchange in Boa constrictor amaralis and Crotalus durissus (Squamata: Serpentes).

Ventilation and gas exchange have been studied in relatively few species of snakes, especially regarding their response to environmental hypoxia or hypercarbia. We exposed Crotalus durissus (N = 6) and Boa constrictor (N = 6) to decreasing levels of oxygen (12, 9, 6, 3 % O2) and increasing levels of carbon dioxide (1.5, 3.0, 4.5, 6.0 % CO2) and analyzed the effect of the different gas mixtures on ventilation and gas exchange using open-flow respirometry. Neither hypoxia nor hypercarbia significantly altered the duration of expiration or inspiration, nor their proportions. Both hypoxia and hypercarbia increased minute ventilation, but the decrease in oxygen had a less pronounced effect on ventilation. Gas exchange under normoxic conditions was low and was not significantly affected by hypoxia, but hypercarbia decreased gas exchange significantly in both species. While B. constrictor maintained its respiratory exchange ratio (RER) under hypercarbia between 0.5 and 1.0, C. durissus showed a RER above 1.0 during hypercarbia, due to a significantly greater CO2 excretion. The overall responses of both species to hypercarbia and especially to hypoxia were very similar, which could be associated to similar lifestyles as ambush hunting sit-and-wait predators that are able to ingest large prey items. The observed differences in gas exchange could be related to respiratory systems with macroscopically different structures, possessing only a tracheal lung in C. durissus, but two functional lungs in B. constrictor.