Serotonergic neurons in the nucleus raphe obscurus contribute to interaction between central and peripheral ventilatory responses to hypercapnia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ventilatory responses to skin extract in catfish

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Orexin in the toad Rhinella schneideri: The location of orexinergic neurons and the role of orexin in ventilatory responses to hypercarbia and hypoxia

Recent reports have suggested that orexins, also known as hypocretins, play an important role in the modulation of respiratory control in mammals, but there are no data available describing the role of the orexinergic system in the peripheral and central chemoreception of non-mammalian vertebrates. Therefore, the present study was designed to examine the localization of orexin-immunoreactive neurons in the brain of toads (Rhinella schneideri) and to investigate the contribution of orexin receptor-1 (OX1R) to the hypoxic and hypercarbic ventilatory responses of these animals during light and dark phases. Our results demonstrated that the orexinergic neurons of R. schneideri are located in the suprachiasmatic nucleus of the diencephalon. Additionally, the intracerebroventricular injection of SB-334867 (OX1R selective antagonist) attenuated the ventilatory response to hypercarbia during the dark phase by acting on tidal volume and breathing frequency, while during the light phase, SB-334867 attenuated the ventilatory response to hypoxia by acting on tidal volume only. We conclude that in the toad R. schneideri, orexinergic neurons are located in the suprachiasmatic nucleus and that OX1R contributes to hypercarbic and hypoxic chemoreflexes.

Hypoxic and hypercapnic ventilatory responses in rats with polycystic ovaries

In female rats, a single injection of estradiol valerate (EV) results in effects that are similar to those observed in women with polycystic ovary syndrome (PCOS). We hypothesized that EV-induced PCOS affects breathing control based on evidence showing an influence of sex hormones on ventilation. To test this hypothesis, we studied the effects of EV treatment on the ventilation of female rats in air, in 7% CO2 and in 7% O2, at 30, 45 and 60 days after EV injection. The group examined 30 days after EV treatment showed a 61% reduction in the hypercapnic ventilatory response compared to the control group. Basal ventilation, hypoxic ventilatory response, and body temperature were not affected. These results, suggest that the hormonal changes observed in PCOS may result in a temporary inhibition of the central chemoreflex but do not influence basal ventilation or the hypoxic peripheral chemoreflex.

Ventilatory responses to skin extract in catfish

The ventilation rate (VR) of an ostariophysan fish, the speckled catfish Pseudoplaty - stoma coruscans, exposed to a chemical alarm cue was measured in the present study in multiple contexts. The influence of the extraction techniques, skin donor food intake and quantity of the alarm cue (skin extract) on this autonomic response was considered. Overall, the catfish VR decreased significantly when exposed to the skin extract (chemical alarm cue) compared with exposure to distilled water (control). No effect of the extraction technique was found. Increasing doses of the skin extract induced a VR reduction of similar magnitude. However, extract obtained from daily-fed fish induced a significant decrease in the VR, whereas extract obtained from foodrestricted fish did not induce any change in the VR. Thus, food intake was associated with the production of a more easily recognizable alarm cue in the speckled catfish. Interestingly, this effect was not related to differences in the number of club cells in the donor catfish epidermis. Dashing, or rapid swimming, a normal component of the alarm response in fish, including this catfish species, was not observed here, and hypoventilation was always associated with no swimming reaction. Together, these results suggest that hypoventilation is a reaction to a chemical alarm cue, likely resulting in improved crypsis, causing the fish to become less easily perceived by a potential predator that usually strikes prey in response to movement.

Ventilatory responses of healthy subjects to intravenous combinations of morphine and oxycodone under imposed hypercapnic and hypoxaemic conditions

Aims Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to healthy human subjects. Methods A placebo-controlled, randomized, crossover study was performed in 12 male volunteers. Ventilatory responses to hypoxaemia and hypercapnia were determined from 1-h intravenous infusions of saline ('placebo'), 15 mg morphine sulphate (M), 15 mg oxycodone hydrochloride (O), and their combination in the dose ratios of 1 : 2, 1 : 1, 2 : 1. Drug and metabolite concentrations in serial peripheral venous blood samples were measured by high-performance liquid chromatography-MS/MS. Results 'Placebo' treatment was without significant ventilatory effects. There were no systematic differences between active drug treatments on either the slopes or intercepts of the hypoxaemic and hypercapnia ventilation responses. During drug treatment, the mean minute ventilation at PETCO2 = 55 mmHg (V-E55) decreased to 74% of the subjects' before treatment values (95% confidence interval 62, 87), 68% (57, 80), 69% (59, 79), 68% (63, 73), and 61% (52, 69) for M15, M10/O5, M7.5/O7.5, M5/O10 and O15, respectively. Recovery was more prolonged with increasing oxycodone doses, corresponding to its greater potency and lower clearance compared with morphine. Conclusions Although adverse ventilatory effects of these drugs were found as expected, no unexpected or disproportionate effects of any of the morphine and oxycodone treatments were found that might impede their use in combination for pain management.

Serotonergic neurons in the nucleus raphé obscurus are not involved in the ventilatory and thermoregulatory responses to hypoxia in adult rats

The medullary raphé is an important component of the central respiratory network, playing a key role in CO2 central chemoreception. However, its participation in hypoxic ventilatory responses is less understood. In the present study, we assessed the role of nucleus raphé obscurus (ROb), and specifically 5-HT neurons confined in the ROb, on ventilatory and thermoregulatory responses to hypoxia. Chemical lesions of the ROb were performed using either ibotenic acid (non-specific lesion; control animals received PBS) or anti-SERT-SAP (5-HT specific lesion; control animals received IgG-SAP). Ventilation (VE; whole body plethysmograph) and body temperature (Tb; data loggers) were measured during normoxia (21% O2, N2 balance) and hypoxia exposure (7% O2, N2 balance, 1h) in conscious adult rats. Ibotenic acid or anti-SERT-SAP-induced lesions did not affect baseline values of VE and Tb. Similarly, both lesion procedures did not alter the ventilatory or thermoregulatory responses to hypoxia. Although evidence in the literature suggests a role of the rostral medullary raphé in hypoxic ventilatory responses, under the present experimental conditions our data indicate that caudal medullary raphé (ROb) and its 5-HT neurons neither participate in the tonic maintenance of breathing nor in the ventilatory and thermal responses to hypoxia. © 2013 Elsevier B.V.

Ventilatory, metabolic, and thermal responses to hypercapnia in female rats: effects of estrous cycle, ovariectomy, and hormonal replacement

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Periaqueductal gray matter modulates the hypercapnic ventilatory response

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The breathing pattern and the ventilatory response to aquatic and aerial hypoxia and hypercarbia in the frog Pipa carvalhoi

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Central leptin replacement enhances chemorespiratory responses in leptin-deficient mice independent of changes in body weight

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The breathing pattern and the ventilatory response to aquatic and aerial hypoxia and hypercarbia in the frog Pipa carvalhoi

Anuran amphibians are known to exhibit an intermittent pattern of pulmonary ventilation and to exhibit an increased ventilatory response to hypoxia and hypercarbia. However, only a few species have been studied to date. The aquatic frog Pipa carvalhoi inhabits lakes, ponds and marshes that are rich in nutrients but low in O-2. There are no studies of the respiratory pattern of this species and its ventilation during hypoxia or hypercarbia. Accordingly, the aim of the present study was to characterize the breathing pattern and the ventilatory response to aquatic and aerial hypoxia and hypercarbia in this species. With this purpose, pulmonary ventilation (V-1) was directly measured by the pneumotachograph method during normocapnic normoxia to determine the basal respiratory pattern and during aerial and aquatic hypercarbia (5% CO2) and hypoxia (5% O-2). Our data demonstrate that P. carvalhoi exhibits a periodic breathing pattern composed of single events (single breaths) of pulmonary ventilation separated by periods of apnea. The animals had an enhanced V-1 during aerial hypoxia, but not during aquatic hypoxia. This increase was strictly the result of an increase in the breathing frequency. A pronounced increase in V-1 was observed if the animals were simultaneously exposed to aerial and aquatic hypercarbia, whereas small or no ventilatory responses were observed during separately administered aerial or aquatic hypercarbia. P. carvalhoi primarily inhabits an aquatic environment. Nevertheless, it does not respond to low O-2 levels in water, although it does so in air. The observed ventilatory responses to hypercarbia may indicate that this species is similar to other anurans in possessing central chemoreceptors. (C) 2012 Elsevier Inc. All rights reserved.