CO2 dialysis in nucleus tractus solitarius region of rat increases ventilation in sleep and wakefulness

2002 ◽  
Vol 92 (5) ◽  
pp. 2119-2130 ◽  
Author(s):  
Eugene E. Nattie ◽  
Aihua Li
Keyword(s):  
Cerebrospinal Fluid ◽  
Tidal Volume ◽  
Nucleus Tractus Solitarius ◽  
Ventilation Frequency ◽  
Retrotrapezoid Nucleus ◽  
Naturally Occurring ◽  
Central Chemoreceptors ◽  
Artificial Cerebrospinal Fluid ◽  
Medullary Raphe ◽  
Stimulation Of

To evaluate the function of widely distributed central chemoreceptors during sleep and wakefulness in the rat, we focally stimulate single chemoreceptor sites during naturally occurring sleep-wake cycles by microdialysis of artificial cerebrospinal fluid equilibrated with 25% CO2. In retrotrapezoid nucleus, this increased ventilation (tidal volume) by 24% only in wakefulness (Li A, Randall M, and Nattie E. J Appl Physiol 87: 910–919, 1999). In caudal medullary raphé, it increased ventilation (frequency) by 15–20% only in sleep (Nattie EE and Li A. J Appl Physiol 90: 1247–1257, 2001). Here, in nucleus tractus solitarius (NTS), focal acidification significantly increased ventilation by 11% in sleep and 7% in wakefulness rostrally ( n = 5) and by 16% in sleep and 28% in wakefulness caudally ( n = 5). The sleep-wake cycle was unaltered. Dialysis with 5% CO2 had no effect. Dialysis with 50% CO2 caudally did not further stimulate ventilation but did disrupt sleep. Central chemoreceptors in the NTS affect breathing in both sleep and wakefulness. The threshold for arousal in caudal NTS is greater than that for the stimulation of breathing.

scholarly journals TRH microdialysis into the RTN of the conscious rat increases breathing, metabolism, and temperature

1999 ◽  
Vol 87 (2) ◽  
pp. 673-682 ◽  
Author(s):  
Carlos Cream ◽  
Eugene Nattie ◽  
Aihua Li
Keyword(s):  
Cerebrospinal Fluid ◽  
Rectal Temperature ◽  
Random Order ◽  
Conscious Rat ◽  
Tissue Volume ◽  
Retrotrapezoid Nucleus ◽  
Sustained Effects ◽  
Artificial Cerebrospinal Fluid ◽  
E 32 ◽  
Stimulation Of

Thyrotropin-releasing hormone (TRH) injected into the retrotrapezoid nucleus (RTN) of anesthetized rats produces a large, prolonged stimulation of ventilatory output (C. L. Cream, A. Li, and E. E. Nattie. J. Appl. Physiol. 83: 792–799, 1997). Here we inject or dialyze TRH into the RTN of conscious rats. In 6 of 17 injections (200 nl, 3.1 ± 1.7 mM), ventilation (V˙e) increased 31% by 10 min, with recovery by 60 min. With dialysis, each animal of one group ( n = 5) received, in random order, 10 mM TRH, 10 mM TRHOH (a metabolite of TRH), and artificial cerebrospinal fluid (aCSF); each animal of a second group ( n = 5) received aCSF and 1 mM TRH. TRHOH and aCSF had no sustained effects. TRH (1 mM) increasedV˙e (32%, P < 0.02, by 10 min, with recovery by 60 min), O2 consumption (V˙o 2; 19%, P < 0.03), and body (rectal) temperature (Tre; 0.5°C, P < 0.09). TRH (10 mM) increasedV˙e (78%, P < 0.01, by 10 min, with no recovery at 60 min), V˙o 2(48%, P < 0.01), and Tre (1.0°C, P < 0.01). TRH also induced arousal. The tissue volume affected in dialysis, estimated by spread of dialyzed fluorescein (332.3 mol wt, mol wt of TRH = 362.4), was 1,580 ± 256 nl for 10 mM ( n = 5) and 590 ± 128 nl for 1 mM ( n = 5). We conclude that 1) the RTN is involved in the integration ofV˙e,V˙o 2, Tre, and arousal and 2) TRH may establish the responsiveness of RTN neurons.

CO2 dialysis in the medullary raphe of the rat increases ventilation in sleep

2001 ◽  
Vol 90 (4) ◽  
pp. 1247-1257 ◽  
Author(s):  
Eugene E. Nattie ◽  
Aihua Li
Keyword(s):  
Eye Movement ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Arousal State ◽  
Retrotrapezoid Nucleus ◽  
Central Chemoreceptors ◽  
Artificial Cerebrospinal Fluid ◽  
Medullary Raphe ◽  
Tissue Acidosis ◽  
End Tidal

Central chemoreceptors are widespread within the brain stem. We hypothesize that function at different sites varies with arousal state. In unanesthetized rats, we produced focal acidification at single sites by means of microdialysis using artificial cerebrospinal fluid equilibrated with 25% CO2. Tissue acidosis, measured under anesthesia, is equivalent to that observed with 63 Torr end-tidal Pco 2 and is limited to 600 μm. Focal acidification of the retrotrapezoid nucleus increased ventilation by 24% only in wakefulness via an increase in tidal volume (Li A, Randall M, and Nattie E. J Appl Physiol 87: 910–919, 1999). In this study of the medullary raphe, the effect of such focal acidification was in sleep (defined by electroencephalographic and electromyographic criteria): ventilation and frequency increased by 15–20% in non-rapid eye movement sleep, and frequency increased by 15% in rapid eye movement sleep. There was no effect in wakefulness. Chemoreception in the medullary raphe appears to be responsive in sleep. Central chemoreceptors at two different locations appear to vary in effectiveness with arousal state.

scholarly journals Focal CO2 dialysis in raphe obscurus does not stimulate ventilation but enhances the response to focal CO2 dialysis in the retrotrapezoid nucleus

2008 ◽  
Vol 105 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Mirela Barros Dias ◽  
Aihua Li ◽  
Eugene Nattie
Keyword(s):  
Cerebrospinal Fluid ◽  
Tidal Volume ◽  
Adult Male ◽  
Male Rats ◽  
Whole Body ◽  
Breathing Frequency ◽  
Retrotrapezoid Nucleus ◽  
Artificial Cerebrospinal Fluid ◽  
Simultaneous Inhibition ◽  
Central Chemoreception

Simultaneous inhibition of the retrotrapezoid nucleus (RTN) and raphe obscurus (ROb) decreased the systemic CO2 response by 51%, an effect greater than inhibition of RTN (−24%) or ROb (0%) alone, suggesting that ROb modulates chemoreception by interaction with the RTN ( 19 ). We investigated this interaction further by simultaneous dialysis of artificial cerebrospinal fluid equilibrated with 25% CO2 in two probes located in or adjacent to the RTN and ROb in conscious adult male rats. Ventilation was measured in a whole body plethysmograph at 30°C. There were four groups ( n = 5): 1) probes correctly placed in both RTN and ROb (RTN-ROb); 2) one probe correctly placed in RTN and one incorrectly placed in areas adjacent to ROb (RTN-peri-ROb); 3) one probe correctly placed in ROb and one probe incorrectly placed in areas adjacent to RTN (peri-RTN-ROb); and 4) neither probe correctly placed (peri-RTN-peri-ROb). Focal simultaneous acidification of RTN-ROb significantly increased ventilation (V̇e) up to 22% compared with baseline, with significant increases in both breathing frequency and tidal volume. Focal acidification of RTN-peri-ROb increased V̇e significantly by up to 15% compared with baseline. Focal acidification of ROb and peri-RTN had no significant effect. The simultaneous acidification of regions just outside the RTN and ROb actually decreased V̇e by up to 11%. These results support a modulatory role for the ROb with respect to central chemoreception at the RTN.

scholarly journals Muscimol dialysis in the retrotrapezoid nucleus region inhibits breathing in the awake rat

2000 ◽  
Vol 89 (1) ◽  
pp. 153-162 ◽  
Author(s):  
Eugene Nattie ◽  
Aihua Li
Keyword(s):  
Cerebrospinal Fluid ◽  
Oxygen Consumption ◽  
Body Temperature ◽  
Tidal Volume ◽  
Physiological Response ◽  
Conscious Rats ◽  
Retrotrapezoid Nucleus ◽  
Artificial Cerebrospinal Fluid ◽  
Awake Rat ◽  
Related Increase

Under anesthesia, inactivation of the retrotrapezoid nucleus (RTN) region markedly inhibits breathing and chemoreception. In conscious rats, we dialyzed muscimol for 30 min to inhibit neurons of the RTN region reversibly. Dialysis of artificial cerebrospinal fluid had no effect. Muscimol (1 or 10 mM) significantly decreased tidal volume (Vt) (by 16–17%) within 15 min. Vt remained decreased for 50 min or more, with recovery by 90 min. Ventilation (V˙e) decreased significantly (by 15–20%) within 15 min and then returned to baseline within 40 min as a result of an increase in frequency. This, we suggest, is a compensatory physiological response to the reduced Vt. Oxygen consumption was unchanged. In response to 7% CO2 in the 1 mM group, absolute V˙e and change in V˙e were significantly reduced (by 19–22%). In the 10 mM group, the response to dialysis included a time-related increase in frequency and decrease in body temperature, which may reflect greater spread of muscimol. In the awake rat, the RTN region provides a portion of the tonic drive to breathe, as well as a portion of the response to hypercapnia.

Ventilatory effects of gap junction blockade in the RTN in awake rats

2004 ◽  
Vol 287 (6) ◽  
pp. R1407-R1418 ◽  
Author(s):  
Amy Hewitt ◽  
Rachel Barrie ◽  
Michael Graham ◽  
Kara Bogus ◽  
J. C. Leiter ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Gap Junctions ◽  
Tidal Volume ◽  
Mineralocorticoid Receptor ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Retrotrapezoid Nucleus ◽  
Artificial Cerebrospinal Fluid ◽  
Ventilatory Effects ◽  
Awake Rats

We tested the hypothesis that carbenoxolone, a pharmacological inhibitor of gap junctions, would reduce the ventilatory response to CO2 when focally perfused within the retrotrapezoid nucleus (RTN). We tested this hypothesis by measuring minute ventilation (VE), tidal volume (VT), and respiratory frequency (FR) responses to increasing concentrations of inspired CO2 (FiCO2 = 0–8%) in rats during wakefulness. We confirmed that the RTN was chemosensitive by perfusing the RTN unilaterally with either acetazolamide (AZ; 10 μM) or hypercapnic artificial cerebrospinal fluid equilibrated with 50% CO2 (pH ∼6.5). Focal perfusion of AZ or hypercapnic aCSF increased VE, VT, and FR during exposure to room air. Carbenoxolone (300 μM) focally perfused into the RTN decreased VE and VT in animals <11 wk of age, but VE and VT were increased in animals >12 wk of age. Glyzyrrhizic acid, a congener of carbenoxolone, did not change VE, VT, or FR when focally perfused into the RTN. Carbenoxolone binds to the mineralocorticoid receptor, but spironolactone (10 μM) did not block the disinhibition of VE or VT in older animals when combined with carbenoxolone. Thus the RTN is a CO2 chemosensory site in all ages tested, but the function of gap junctions in the chemosensory process varies substantially among animals of different ages: gap junctions amplify the ventilatory response to CO2 in younger animals, but appear to inhibit the ventilatory response to CO2 in older animals.

scholarly journals Noradrenergic control of central oxytocin release during lactation in rats

1998 ◽  
Vol 274 (3) ◽  
pp. E453-E458 ◽  
Author(s):  
Steven L. Bealer ◽  
William R. Crowley
Keyword(s):  
Cerebrospinal Fluid ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Additional Experiment ◽  
Adrenergic Agonist ◽  
Magnocellular Nuclei ◽  
Artificial Cerebrospinal Fluid ◽  
Oxytocin Release ◽  
Stimulation Of

Noradrenergic systems regulate the systemic release of oxytocin (OT) in lactating rats. However, a role for norepinephrine (NE) in release of OT within the magnocellular nuclei during suckling has not been established. These studies were designed to determine 1) if suckling induces NE release in the supraoptic (SON) and paraventricular (PVN) nuclei of conscious rats and 2) the role of NE in the central, intranuclear release of OT within these nuclei. Female Holtzman rats were implanted with microdialysis probes adjacent to the PVN or SON on lactation days 8- 12. The following day, the pups were isolated from the dams for 4 h. Microdialysis probes were perfused with artificial cerebrospinal fluid (ACSF) or with ACSF containing an α- or a β-adrenergic receptor antagonist. Dialysate was collected before, during, and after suckling and analyzed for NE or OT. In an additional experiment, an α- or β-adrenergic agonist was administered via the microdialysis probes into the PVN in nonsuckled, lactating rats. Extracellular NE increased in the PVN during suckling but was not detectable in the SON. OT concentrations in dialysates from the PVN and SON significantly increased during suckling. Blockade of either α- (in both PVN and SON) or β- (PVN) adrenergic receptors prevented the suckling-induced increase in central OT release. OT release was increased in nonsuckled, lactating rats by central application of either an α- or β-adrenergic agonist. These data demonstrate that intranuclear NE release is increased in the PVN by suckling and that subsequent stimulation of both α- and β-noradrenergic receptors mediates intranuclear OT release.

Selective enhancement in SHR of hypotension and bradycardia caused by NTS-injected serotonin

1994 ◽  
Vol 266 (2) ◽  
pp. R599-R605 ◽  
Author(s):  
M. Okada ◽  
R. D. Bunag
Keyword(s):  
Cerebrospinal Fluid ◽  
Spontaneously Hypertensive Rats ◽  
Nucleus Tractus Solitarius ◽  
Isotonic Saline ◽  
Hypertensive Rats ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Spontaneously Hypertensive ◽  
Artificial Cerebrospinal Fluid ◽  
Renal Nerve Activity

To examine whether serotonergic mechanisms in the nucleus tractus solitarius (NTS) become altered by hypertension, responses to serotonin (5-HT) or L-glutamate injected into the NTS were compared in anesthetized rats. Because isotonic saline had appreciable effects whereas artificial cerebrospinal fluid did not, artificial cerebrospinal fluid was routinely used as the vehicle. Microinjections of 5-HT or L-glutamate always reduced mean pressure, heart rate, and renal nerve activity. Depressor and bradycardic responses to 5-HT were consistently more pronounced in spontaneously hypertensive rats than in either regular Wistar or Wistar-Kyoto rats, but similar responses elicited with L-glutamate did not differ between rat groups. By contrast, attendant inhibition of renal nerve activity was the same in all rats, thereby suggesting that it either is not a good indicator of sympathetic activity or does not contribute to the hypotensive effects of 5-HT. Our results are compatible with the interpretation that hypotensive responses to 5-HT were enhanced because serotonergic mechanisms for cardiovascular regulation in the NTS were sensitized in spontaneously hypertensive rats.

Chronic fluoxetine microdialysis into the medullary raphe nuclei of the rat, but not systemic administration, increases the ventilatory response to CO2

2004 ◽  
Vol 97 (5) ◽  
pp. 1763-1773 ◽  
Author(s):  
Natalie C. Taylor ◽  
Aihua Li ◽  
Adam Green ◽  
Hannah C. Kinney ◽  
Eugene E. Nattie
Keyword(s):  
Tidal Volume ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Repeated Administration ◽  
Fluoxetine Treatment ◽  
Artificial Cerebrospinal Fluid ◽  
Medullary Raphe ◽  
Chronic Fluoxetine ◽  
Serotonergic Function ◽  
Ventilatory Response To Co2

In conscious rats, focal CO2 stimulation of the medullary raphe increases ventilation, whereas interference with serotonergic function here decreases the ventilatory response to systemic hypercapnia. We sought to determine whether repeated administration of a selective serotonin reuptake inhibitor in this region would increase the ventilatory response to hypercapnia in unanesthetized rats. In rats instrumented with electroencephalogram-electromyogram electrodes, 250 or 500 μM fluoxetine or artificial cerebrospinal fluid (aCSF) was microdialyzed into the medullary raphe for 30 min daily over 15 days. To compare focal and systemic treatment, two additional groups of rats received 10 mg·kg−1·day−1 fluoxetine or vehicle systemically. Ventilation was measured in normocapnia and in 7% CO2 before treatment ( day 0), acutely ( days 1 or 3), on day 7, and on day 15. There was no change in normocapnic ventilation in any treatment group. Rats that received 250 μM fluoxetine microdialysis showed a significant 13% increase in ventilation in wakefulness during hypercapnia on day 7, due to an increase in tidal volume. In rats microdialyzed with 500 μM fluoxetine, there were 16 and 32% increases in minute ventilation during hypercapnia in wakefulness and sleep on day 7, and 20 and 28% increases on day 15, respectively, again due to increased tidal volume. There was no change in the ventilatory response to CO2 in rats microdialyzed with aCSF or in systemically treated rats. Chronic fluoxetine treatment in the medullary raphe increases the ventilatory response to hypercapnia in an unanesthetized rat model, an effect that may be due to facilitation of chemosensitive serotonergic neurons.

Composition of cerebral fluids in goats adapted to high altitude

1979 ◽  
Vol 47 (3) ◽  
pp. 508-513 ◽  
Author(s):  
V. Fencl ◽  
R. A. Gabel ◽  
D. Wolfe
Keyword(s):  
Cerebrospinal Fluid ◽  
High Altitude ◽  
Sea Level ◽  
Interstitial Fluid ◽  
Ionic Composition ◽  
Central Chemoreceptors ◽  
Alkaline Shift ◽  
Artificial Cerebrospinal Fluid ◽  
Simulated High Altitude

We explored the ionic composition of cerebral interstitial fluid (cISF) in six unanesthetized goats at sea level (SL) and again after 5 days at a simulated high altitude (HA) of 4,300 m. By measuring net transependymal fluxes of HCO3-, Cl-, and lactate during ventriculocisternal perfusions with lactate-free artificial cerebrospinal fluid (CSF) with various [HCO3-] and [Cl-], we determined [HCO3-] and [Cl-] in the inflowing perfusate that produced zero flux, which are estimates of the concentrations of these ions in cISF. Ventilatory acclimatization to HA was established in the goats with alkaline shift in cisternal CSF pH. At SL zero flux of HCO3- and of Cl- occurred when [HCO3-] and [Cl-] in the perfusate were equal to those in CSF. At HA Cl- flux again was zero when [Cl-] in perfusate and in the goat's own CSF were equal; however, for HCO3-, zero flux occurred at HA when [HCO3-] in perfusate was significantly lower than in CSF. Mean transependymal washout of lactate was 16 times larger at HA than at SL. We conclude that at SL [HCO3-] and [Cl-] in CSF were the same as in cISF. In goats adapted to HA [Cl-] in cISF and in CSF were again equal, whereas [HCO3-] in cISF was lower and [lactate] presumably higher than in CSF. The fluid surrounding the central chemoreceptors appears to be more acidic in goats acclimatized to HA than at SL despite the alkalosis in cisternal CSF. This may contribute to ventilatory acclimatization to HA.

Lowering calcium in the nucleus tractus solitarius causes hypotension and bradycardia

1986 ◽  
Vol 250 (2) ◽  
pp. H226-H230 ◽  
Author(s):  
S. Higuchi ◽  
A. Takeshita ◽  
H. Higashi ◽  
N. Ito ◽  
T. Imaizumi ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cerebrospinal Fluid ◽  
Arterial Pressure ◽  
Calcium Ions ◽  
Nucleus Tractus Solitarius ◽  
Anesthetized Rats ◽  
Artificial Cerebrospinal Fluid ◽  
The Difference

It has been shown that saline microinjected into the region of the nucleus tractus solitarius (NTS) causes, but artificial cerebrospinal fluid (CSF) in the same volume does not cause, hypotension and bradycardia. This study was done to examine the possibility that the difference in effects between saline and artificial CSF may be due to the lack of calcium ions in saline. In anesthetized rats, saline or artificial CSF with or without calcium ions was microinjected into the region of the NTS. Saline microinjected in volumes of 0.2 and 0.5 microliter produced the volume-dependent decreases in arterial pressure and heart rate. Saline with added calcium ions and artificial CSF did not elicit the hypotensive and bradycardic response, but artificial CSF without calcium ions produced hypotension and bradycardia. These results suggest that the lack of calcium ions in the injected solutions is the factor that determines the hypotensive and bradycardic response. These results suggest that lowering the local availability of calcium to the NTS neurons results in hypotension and bradycardia.

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