scholarly journals Catecholaminergic neurons projecting to the paraventricular nucleus of the hypothalamus are essential for cardiorespiratory adjustments to hypoxia

2015 ◽  
Vol 309 (7) ◽  
pp. R721-R731 ◽  
Author(s):  
T. Luise King ◽  
Brian C. Ruyle ◽  
David D. Kline ◽  
Cheryl M. Heesch ◽  
Eileen M. Hasser
Keyword(s):  
Paraventricular Nucleus ◽  
Minute Ventilation ◽  
Sensory Information ◽  
Ventrolateral Medulla ◽  
Arterial Oxygen ◽  
Catecholaminergic Neurons ◽  
Ventilatory Responses ◽  
Cardiorespiratory Function ◽  
Neuroendocrine Responses ◽  
Catecholamine Neurons

Brainstem catecholamine neurons modulate sensory information and participate in control of cardiorespiratory function. These neurons have multiple projections, including to the paraventricular nucleus (PVN), which contributes to cardiorespiratory and neuroendocrine responses to hypoxia. We have shown that PVN-projecting catecholaminergic neurons are activated by hypoxia, but the function of these neurons is not known. To test the hypothesis that PVN-projecting catecholamine neurons participate in responses to respiratory challenges, we injected IgG saporin (control; n = 6) or anti-dopamine β-hydroxylase saporin (DSAP; n = 6) into the PVN to retrogradely lesion catecholamine neurons projecting to the PVN. After 2 wk, respiratory measurements (plethysmography) were made in awake rats during normoxia, increasing intensities of hypoxia (12, 10, and 8% O2) and hypercapnia (5% CO2-95% O2). DSAP decreased the number of tyrosine hydroxylase-immunoreactive terminals in PVN and cells counted in ventrolateral medulla (VLM; −37%) and nucleus tractus solitarii (nTS; −36%). DSAP produced a small but significant decrease in respiratory rate at baseline (during normoxia) and at all intensities of hypoxia. Tidal volume and minute ventilation (VE) index also were impaired at higher hypoxic intensities (10-8% O2; e.g., VE at 8% O2: IgG = 181 ± 22, DSAP = 91 ± 4 arbitrary units). Depressed ventilation in DSAP rats was associated with significantly lower arterial O2 saturation at all hypoxic intensities. PVN DSAP also reduced ventilatory responses to 5% CO2 (VE: IgG = 176 ± 21 and DSAP = 84 ± 5 arbitrary units). Data indicate that catecholamine neurons projecting to the PVN are important for peripheral and central chemoreflex respiratory responses and for maintenance of arterial oxygen levels during hypoxic stimuli.

scholarly journals Acute systemic hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the caudal ventrolateral medulla

2013 ◽  
Vol 305 (10) ◽  
pp. R1112-R1123 ◽  
Author(s):  
T. Luise King ◽  
David D. Kline ◽  
Brian C. Ruyle ◽  
Cheryl M. Heesch ◽  
Eileen M. Hasser
Keyword(s):  
Paraventricular Nucleus ◽  
Acute Hypoxia ◽  
Hypothalamic Paraventricular Nucleus ◽  
Ventrolateral Medulla ◽  
Caudal Ventrolateral Medulla ◽  
Catecholaminergic Neurons ◽  
Systemic Hypoxia ◽  
Neuroendocrine Responses ◽  
Catecholamine Neurons ◽  
Catecholaminergic Cells

Hypoxia activates catecholamine neurons in the caudal ventrolateral medulla (CVLM). The hypothalamic paraventricular nucleus (PVN) modulates arterial chemoreflex responses and receives catecholaminergic projections from the CVLM, but it is not known whether the CVLM-PVN projection is activated by chemoreflex stimulation. We hypothesized that acute hypoxia (AH) activates PVN-projecting catecholaminergic neurons in the CVLM. Fluoro-Gold (2%, 60–90 nl) was microinjected into the PVN of rats to retrogradely label CVLM neurons. After recovery, conscious rats underwent 3 h of normoxia (21% O2, n = 4) or AH (12, 10, or 8% O2; n = 5 each group). We used Fos immunoreactivity as an index of CVLM neuronal activation and tyrosine hydroxylase (TH) immunoreactivity to identify catecholaminergic neurons. Positively labeled neurons were counted in six caudal-rostral sections containing CVLM. Hypoxia progressively increased the number of Fos-immunoreactive CVLM cells (21%, 19 ± 6; 12%, 49 ± 2; 10%, 117 ± 8; 8%, 179 ± 7; P < 0.001). Catecholaminergic cells colabeled with Fos immunoreactivity in the CVLM were observed following 12% O2, and further increases in hypoxia severity caused markedly more activation. PVN-projecting CVLM cells were activated following more severe hypoxia (10% and 8% O2). A large proportion (89 ± 3%) of all activated PVN-projecting CVLM neurons were catecholaminergic, regardless of hypoxia intensity. Data suggest that catecholaminergic, PVN-projecting CVLM neurons are particularly hypoxia-sensitive, and these neurons may be important in the cardiorespiratory and/or neuroendocrine responses elicited by the chemoreflex.

scholarly journals Hypoxia activates nucleus tractus solitarii neurons projecting to the paraventricular nucleus of the hypothalamus

2012 ◽  
Vol 302 (10) ◽  
pp. R1219-R1232 ◽  
Author(s):  
T. Luise King ◽  
Cheryl M. Heesch ◽  
Catharine G. Clark ◽  
David D. Kline ◽  
Eileen M. Hasser
Keyword(s):  
Arterial Pressure ◽  
Paraventricular Nucleus ◽  
Acute Hypoxia ◽  
Brain Regions ◽  
Nucleus Tractus Solitarii ◽  
Ventrolateral Medulla ◽  
Peripheral Chemoreceptor ◽  
Cardiorespiratory Function ◽  
Afferent Information ◽  
Fos Expression

Peripheral chemoreceptor afferent information is sent to the nucleus tractus solitarii (nTS), integrated, and relayed to other brain regions to alter cardiorespiratory function. The nTS projects to the hypothalamic paraventricular nucleus (PVN), but activation and phenotype of these projections during chemoreflex stimulation is unknown. We hypothesized that activation of PVN-projecting nTS neurons occurs primarily at high intensities of hypoxia. We assessed ventilation and cardiovascular parameters in response to increasing severities of hypoxia. Retrograde tracers were used to label nTS PVN-projecting neurons and, in some rats, rostral ventrolateral medulla (RVLM)-projecting neurons. Immunohistochemistry was performed to identify nTS cells that were activated (Fos-immunoreactive, Fos-IR), catecholaminergic, and GABAergic following hypoxia. Conscious rats underwent 3 h normoxia ( n = 4, 21% O2) or acute hypoxia (12, 10, or 8% O2; n = 5 each). Hypoxia increased ventilation and the number of Fos-IR nTS cells (21%, 13 ± 2; 12%, 58 ± 4; 10%, 166 ± 22; 8%, 186 ± 6). Fos expression after 10% O2was similar whether arterial pressure was allowed to decrease (−13 ± 1 mmHg) or was held constant. The percentage of PVN-projecting cells activated was intensity dependent, but contrary to our hypothesis, PVN-projecting nTS cells exhibiting Fos-IR were found at all hypoxic intensities. Notably, at all intensities of hypoxia, ∼75% of the activated PVN-projecting nTS neurons were catecholaminergic. Compared with RVLM-projecting cells, a greater percentage of PVN-projecting nTS cells was activated by 10% O2. Data suggest that increasing hypoxic intensity activates nTS PVN-projecting cells, especially catecholaminergic, PVN-projecting neurons. The nTS to PVN catecholaminergic pathway may be critical even at lower levels of chemoreflex activation and more important to cardiorespiratory responses than previously considered.

Substance P in the ventrolateral medulla oblongata regulates ventilatory responses

1990 ◽  
Vol 68 (6) ◽  
pp. 2631-2639 ◽  
Author(s):  
Z. Chen ◽  
J. Hedner ◽  
T. Hedner
Keyword(s):  
Substance P ◽  
Medulla Oblongata ◽  
Nucleus Tractus Solitarius ◽  
Minute Ventilation ◽  
Ventrolateral Medulla ◽  
Cervical Cord ◽  
Co2 Response ◽  
Caudal Region ◽  
Ventilatory Responses ◽  
Cervical Segment

Local injection of substance P (SP) into the ventral portion of the nucleus gigantocellularis, nucleus reticularis lateralis, and nucleus retrofacialis of the ventrolateral medulla oblongata (VLM) or direct application on the ventral surface of the medulla oblongata caused marked stimulation of tidal volume (VT) and/or minute ventilation (VE). The ventilatory response to hypoxia was significantly blunted after SP in the VLM but not in the dorsal medulla oblongata (DM) (nucleus tractus solitarius). The SP antagonist [D-Pro2,D-Trp7,9]SP almost completely inhibited this response when applied locally to a wide area of the superficial layer of the VLM but not of the DM. Unilateral or bilateral application of 0.3-1.5 nmol of the SP antagonist in the VLM (corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment) markedly attenuated the response to a 5% CO2 inhalation. The inhibition of the CO2 response was seen after [D-Pro2,D-Trp7,9]SP in the rostral areas of the medulla oblongata corresponding to the corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment of the cervical cord. Electric somatosensory-induced ventilatory stimulation could be depressed by approximately 70% by [D-Pro2,D-Trp7,9]SP locally applied on the surface of the VLM. We conclude that SP is involved in the hypoxic, hypercapnic, and somatosensory ventilatory responses in the rat. However, these respiratory reflexes are mediated via different neuronal pools in the medulla oblongata, mainly the VLM.

scholarly journals Orexin-A enhances feeding in male rats by activating hindbrain catecholamine neurons

2015 ◽  
Vol 309 (4) ◽  
pp. R358-R367 ◽  
Author(s):  
Ai-Jun Li ◽  
Qing Wang ◽  
Hana Davis ◽  
Rong Wang ◽  
Sue Ritter
Keyword(s):  
Food Intake ◽  
Male Rats ◽  
Ventrolateral Medulla ◽  
Orexin A ◽  
Catecholaminergic Neurons ◽  
Close Proximity ◽  
Cell Groups ◽  
Increase Food Intake ◽  
Catecholamine Neurons ◽  
Positive Direct

Both lateral hypothalamic orexinergic neurons and hindbrain catecholaminergic neurons contribute to control of feeding behavior. Orexin fibers and terminals are present in close proximity to hindbrain catecholaminergic neurons, and fourth ventricular (4V) orexin injections that increase food intake also increase c-Fos expression in hindbrain catecholamine neurons, suggesting that orexin neurons may stimulate feeding by activating catecholamine neurons. Here we examine that hypothesis in more detail. We found that 4V injection of orexin-A (0.5 nmol/rat) produced widespread activation of c-Fos in hindbrain catecholamine cell groups. In the A1 and C1 cell groups in the ventrolateral medulla, where most c-Fos-positive neurons were also dopamine β hydroxylase (DBH) positive, direct injections of a lower dose (67 pmol/200 nl) of orexin-A also increased food intake in intact rats. Then, with the use of the retrogradely transported immunotoxin, anti-DBH conjugated to saporin (DSAP), which targets and destroys DBH-expressing catecholamine neurons, we examined the hypothesis that catecholamine neurons are required for orexin-induced feeding. Rats given paraventricular hypothalamic injections of DSAP, or unconjugated saporin (SAP) as control, were implanted with 4V or lateral ventricular (LV) cannulas and tested for feeding in response to ventricular injection of orexin-A (0.5 nmol/rat). Both LV and 4V orexin-A stimulated feeding in SAP controls, but DSAP abolished these responses. These results reveal for the first time that catecholamine neurons are required for feeding induced by injection of orexin-A into either LV or 4V.

Breathing pattern in humans: elevated CO2 or low O2 on positive airway pressure

1984 ◽  
Vol 56 (3) ◽  
pp. 777-784 ◽  
Author(s):  
J. A. Hirsch ◽  
B. Bishop
Keyword(s):  
Elevated Co2 ◽  
Breathing Pattern ◽  
Minute Ventilation ◽  
Sensory Information ◽  
Positive Pressure ◽  
Ventilatory Responses ◽  
Chemical Stimuli ◽  
The Individual ◽  
End Tidal ◽  
End Tidal Co2

The purpose of this study was to determine effects on breathing pattern of pressure breathing alone and in combination with chemical stimulation. We analyzed ventilatory responses to elevated airway pressures (positive-pressure breathing, PPB) in subjects breathing air, 12% O2, or elevated CO2. Each subject sat in a body box and breathed via mouth-piece from a bag-in-box. Responses to PPB on air were increased minute ventilation (VI), tidal volume (VT), frequency (f), mean inspiratory (VT/TI) and expiratory (VT/TE) flows, decreased expiratory duration (TE) and end-tidal CO2. If end-tidal CO2 were held constant, VI, VT, and VT/TI increased less. Responses greater than predicted from summing responses to either stimulus alone were observed for VT, f, VT/TI, and VT/TE during 3 and 5% CO2 and for VT, f, and VT/TE during isocapnic hypoxia. Responses to other combined stimuli were sums of responses to the individual stimuli. Thus ventilatory responses to combined PPB and chemical stimuli cannot be predicted simply from summating responses to each independently imposed stimulus, suggesting that sensory information arises from and is integrated at multiple sites.

Cardiovascular and ventilatory response to isocapnic hypoxia at sea level and at 5,050 m

1996 ◽  
Vol 80 (5) ◽  
pp. 1724-1730 ◽  
Author(s):  
G. Insalaco ◽  
S. Romano ◽  
A. Salvaggio ◽  
A. Braghiroli ◽  
P. Lanfranchi ◽  
...  
Keyword(s):  
Oxygen Saturation ◽  
Sea Level ◽  
Minute Ventilation ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Ventilatory Responses ◽  
Hypoxic Conditions ◽  
Progressive Hypoxia ◽  
End Tidal ◽  
End Tidal Co2

To assess the effect of chronic hypoxic conditions on ventilatory, heart rate (HR), and blood pressure (BP) responses to acute progressive isocapnic hypoxia, we studied five healthy Caucasian subjects (3 men and 2 women). Each subject performed one rebreathing test at sea level (SL) and two tests at the Pyramid laboratory at Lobuche, Nepal, at the altitude of 5,050 m, 1 day after arrival (HA1) and after 24 days of sojourn (HA2). The effects of progressive isocapnic hypoxia were tested by using a standard rebreathing technique. BP, electrocardiogram, arterial oxygen saturation, airflow and end-tidal CO2 and O2 were recorded. For each subject, the relationships between arterial oxygen saturation and HR, systolic BP and minute ventilation (VE), respectively, were evaluated. At HA1, the majority of subjects showed a significant increase in VE and BP response and a decrease in HR response to progressive isocapnic hypoxia as compared to SL. At HA2, VE and BP responses further increased, whereas the HR response remained similar to that observed at HA1. A significant relationship between hypoxic ventilatory responses and both systolic and diastolic BP responses to progressive hypoxia was found. No significant correlation was found between hypoxic ventilatory and HR responses.

Sexual influence on the control of breathing

1983 ◽  
Vol 54 (4) ◽  
pp. 874-879 ◽  
Author(s):  
D. P. White ◽  
N. J. Douglas ◽  
C. K. Pickett ◽  
J. V. Weil ◽  
C. W. Zwillich
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Premenopausal Women ◽  
Co2 Production ◽  
Menstrual Phase ◽  
Co2 Partial Pressure ◽  
Ventilatory Responses ◽  
Chemical Stimuli ◽  
Low Levels ◽  
Normal Women

Previous investigation has demonstrated that progesterone, a hormone found in premenopausal women, is a ventilatory stimulant. However, fragmentary data suggest that normal women may have lower ventilatory responses to chemical stimuli than men, in whom progesterone is found at low levels. As male-female differences have not been carefully studied, we undertook a systematic comparison of resting ventilation and ventilatory responses to chemical stimuli in men and women. Resting ventilation was found to correlate closely with CO2 production in all subjects (r = 0.71, P less than 0.001), but women tended to have a greater minute ventilation per milliliter of CO2 produced (P less than 0.05) and consequently a lower CO2 partial pressure (PCO2) (men 35.1 +/- 0.5 Torr, women 33.2 +/- 0.5 Torr; P less than 0.02). Women were also found to have lower tidal volumes, even when corrected from body surface area (BSA), and greater respiratory frequency than comparable males. The hypoxic ventilatory response (HVR) quantitated by the shape parameter A was significantly greater in men [167 +/- 22 (SE)] than in women (109 +/- 13; P less than 0.05). In men this hypoxic response was found to correlate closely with O2 consumption (r = 0.75, P less than 0.001) but with no measure of size or metabolic rate in women. The hypercapnic ventilatory response, expressed as the slope of ventilation vs. PCO2, was also greater in men (2.30 +/- 0.23) than in women (1.58 +/- 0.19, P less than 0.05). Finally women tended to have higher ventilatory responses in the luteal than in the follicular menstrual phase, but this was significant only for HVR (P less than 0.05). Women, with relatively higher resting ventilation, have lower responses to hypoxia and hypercapnia.

PERIODIC BREATHING AND APNEA IN PRETERM INFANTS. II. HYPOXIA AS A PRIMARY EVENT

PEDIATRICS ◽  
1972 ◽  
Vol 50 (2) ◽  
pp. 219-228
Author(s):  
Henrique Rigatto ◽  
June P. Brady
Keyword(s):  
Preterm Infants ◽  
Oxygen Tension ◽  
Minute Ventilation ◽  
Arterial Oxygen Tension ◽  
Blood Gases ◽  
Periodic Breathing ◽  
Capillary Blood ◽  
Arterial Oxygen ◽  
Primary Event ◽  
The Relationship

We studied nine healthy preterm infants during the first 35 days of life to define the relationship between periodic breathing, apnea, and hypoxia. For this purpose we compared ventilation/apnea (V/A), minute ventilation, and alveolar and capillary blood gases during periodic breathing induced by hypoxia and during spontancous periodic breathing in room air. We induced periodic breathing by giving the baby in sequence 21, 19, 17, and 15% O2 to breathe for 5 minutes each, and also by giving 21, 15, and 21% O2. We measured ventilation with a nosepiece and a screen flowmeter. With a decrease in arterial oxygen tension, preterm infants (1) hypoventilated, (2) breathed periodically more frequently, and (3) showed a decrease in V/A due to an increase in the apneic interval. In one baby this led to apnea lasting 30 seconds. These findings support our hypothesis that preterm infants breathing periodically hypoventilate and suggest that hypoxia may be a primary event leading to periodic breathing and apnea.

Ventilatory responses to cooling the ventrolateral medullary surface of awake and anesthetized goats

1995 ◽  
Vol 78 (1) ◽  
pp. 247-257 ◽  
Author(s):  
P. J. Ohtake ◽  
H. V. Forster ◽  
L. G. Pan ◽  
T. F. Lowry ◽  
M. J. Korducki ◽  
...  
Keyword(s):  
Pulmonary Ventilation ◽  
Respiratory Rhythm ◽  
Respiratory Neurons ◽  
Ventrolateral Medulla ◽  
Arterial Pco2 ◽  
Respiratory Rhythmogenesis ◽  
Ventilatory Responses ◽  
Anesthesia Breathing ◽  
A Site ◽  
Caudal Area

The ventrolateral medulla (VLM) has been reported to be important as a source of tonic facilitation of dorsal respiratory neurons and as a site critical for respiratory rhythmogenesis. We investigated these theories in awake and anesthetized goats (n = 13) by using chronically implanted thermodes to create reversible neuronal dysfunction at superficial VLM sites between the first hypoglossal rootlet and the pontomedullary junction (area M (rostral) and area S). During halothane anesthesia (arterial PCO2 = 57.4 +/- 4.5 Torr), bilateral cooling (thermode temperature = 20 degrees C) of 60–100% of areas M and S for 30 s produced a sustained apnea (46 +/- 4 s) that lasted beyond the period of cooling. While the animals were awake (arterial PCO2 = 36.0 +/- 1.9 Torr), cooling the identical region in the same goats resulted in a decrease (approximately 50%) in pulmonary ventilation, with a brief apnea seen only in one goat. Reductions in both tidal volume and frequency were observed. Qualitatively similar responses were obtained when cooling caudal area M-rostral area S and rostral area M, but the responses were less pronounced. Minimal effects were seen in response to cooling caudal area S. During anesthesia, breathing is critically dependent on superficial VLM neurons, whereas in the awake state these neurons are not essential for the maintenance of respiratory rhythm. Our data are consistent with these superficial VLM neuronal regions providing tonic facilitation to more dorsal respiratory neurons in both the anesthetized and awake states.

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