scholarly journals Purinergic transmission in the rostral but not caudal medullary raphe contributes to the hypercapnia-induced ventilatory response in unanesthetized rats

2012 ◽  
Vol 184 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Glauber S.F. da Silva ◽  
Davi J.A. Moraes ◽  
Humberto Giusti ◽  
Mirela Barros Dias ◽  
Mogens L. Glass
Keyword(s):  
Ventilatory Response ◽  
Purinergic Transmission ◽  
Medullary Raphe

scholarly journals Activation of Opioid μ Receptors in Caudal Medullary Raphe Region Inhibits the Ventilatory Response to Hypercapnia in Anesthetized Rats

2007 ◽  
Vol 107 (2) ◽  
pp. 288-297 ◽  
Author(s):  
Zhenxiong Zhang ◽  
Fadi Xu ◽  
Cancan Zhang ◽  
Xiaomin Liang
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Central Area ◽  
Mu Receptor ◽  
Medullary Raphe ◽  
Mu Receptors ◽  
End Tidal ◽  
Spontaneously Breathing ◽  
Made In

Background : Opioids, extensively used as analgesics, markedly depress ventilation, particularly the ventilatory responsiveness to hypercapnia in humans and animals predominantly via acting on mu receptors. The medullary raphe region (MRR) contains abundant mu receptors responsible for analgesia and is also an important central area involving carbon dioxide chemoreception and contributing to the ventilatory responsiveness to hypercapnia. Therefore, the authors asked whether activation of mu receptors in the caudal, medial, or rostral MRR depressed ventilation and the response to hypercapnia, respectively. Methods : Experiments were conducted in 32 anesthetized and spontaneously breathing rats. Ventilation and it response to progressive hypercapnia were recorded. The slopes obtained from plotting minute ventilation, respiratory frequency, and tidal volume against the corresponding levels of end-tidal pressure of carbon dioxide were used as the indices of the respiratory responsiveness to carbon dioxide. DAMGO ([d-Ala2, N-Me-Phe4, Gly-ol]-enkephalin), a mu-receptor agonist, was systemically administered (100 mug/kg) before and/or after local injection of CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) (100 ng/100 nl), a mu-receptor antagonist, into the caudal MRR, or locally administered (35 ng/100 nl) into the MRR subnuclei. Results : The authors found that systemic DAMGO significantly inhibited ventilation and the response to carbon dioxide by 20% and 31%, respectively, and these responses were significantly diminished to 11% and 14% after pretreatment of the caudal MRR with CTAP. Local administration of DAMGO into the caudal MRR also reduced ventilation and the response to carbon dioxide by 22% and 28%, respectively. In sharp contrast, these responses were not observed when the DAMGO microinjection was made in the middle MRR or rostral MRR. Conclusions : These results lead to the conclusion that mu receptors in the caudal MRR rather than the middle MRR or rostral MRR are important but not exclusive for attenuating the hypercapnic ventilatory response.

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.

Inhibition of medullary raphé serotonergic neurons has age-dependent effects on the CO2 response in newborn piglets

2004 ◽  
Vol 96 (5) ◽  
pp. 1909-1919 ◽  
Author(s):  
Michelle L. Messier ◽  
Aihua Li ◽  
Eugene E. Nattie
Keyword(s):  
Cerebrospinal Fluid ◽  
Ventilatory Response ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Serotonergic Neurons ◽  
Newborn Piglets ◽  
Artificial Cerebrospinal Fluid ◽  
Age Dependent ◽  
Medullary Raphe ◽  
Raphe Neurons

Medullary raphé serotonergic neurons are chemosensitive in culture and are situated adjacent to blood vessels in the brain stem. Selective lesioning of serotonergic raphé neurons decreases the ventilatory response to systemic CO2 in awake and sleeping adult rats. Abnormalities in the medullary serotonergic system, including the raphé, have been implicated in the sudden infant death syndrome ( 48 ). In this study, we ask whether serotonergic neurons in the medullary raphé and extra-raphé regions are involved in the CO2 response in unanesthetized newborn piglets, 3-16 days old. Whole body plethysmography was used to examine the ventilatory response to 5% CO2 before and during focal inhibition of serotonergic neurons by 8-hydroxy-2-di- n-propylaminotetralin (8-OH-DPAT), a 5-HT1A receptor agonist. 8-OH-DPAT (10 or 30 mM in artificial cerebrospinal fluid) decreased the CO2 response in wakefulness in an age-dependent manner, as revealed by a linear regression analysis that showed a significant negative correlation ( P < 0.001) between the percent change in the CO2 response and piglet age. Younger piglets showed an exaggerated CO2 response. Control dialysis with artificial cerebrospinal fluid had no significant effect on the CO2 response. Additionally, 8-OH-DPAT increased blood pressure and decreased heart rate independent of age ( P < 0.05). Finally, sleep cycling was disrupted by 8-OH-DPAT, such that piglets were awake more and asleep less ( P < 0.05). Because of the fragmentary sleep data, it was not possible to examine the CO2 response in sleep. Inhibition of serotonergic medullary raphé and extra-raphé neurons decreases ventilatory CO2 sensitivity and alters cardiovascular variables and sleep cycling, which may contribute to the sudden infant death syndrome.

Effects on breathing of focal acidosis at multiple medullary raphe sites in awake goats

2004 ◽  
Vol 97 (6) ◽  
pp. 2303-2309 ◽  
Author(s):  
M. R. Hodges ◽  
P. Martino ◽  
S. Davis ◽  
C. Opansky ◽  
L. G. Pan ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cerebral Spinal Fluid ◽  
Ventilatory Response ◽  
Cumulative Effect ◽  
Inspiratory Flow ◽  
Physiological Changes ◽  
Medullary Raphe ◽  
The Brain ◽  
Insight Into ◽  
Thermogenic Response

To gain insight into why there are chemoreceptors at widespread sites in the brain, mircrotubules were chronically implanted at two or three sites in the medullary raphe nuclei of adult goats ( n = 7). After >2 wk, microdialysis (MD) probes were inserted into the microtubules to create focal acidosis (FA) in the awake state using mock cerebral spinal fluid (mCSF) equilibrated with 6.4% (pH = 7.3), 50% (pH = 6.5), or 80% CO2 (pH = 6.3), where MD with 50 and 80% CO2 reduces tissue pH by 0.1 and 0.18 pH unit, respectively. There were no changes in all measured variables with MD with 6.4% at single or multiple raphe sites ( P > 0.05). During FA at single raphe sites, only 80% CO2 elicited physiological changes as inspiratory flow was 16.9% above ( P < 0.05) control. However, FA with 50 and 80% CO2 at multiple sites increased ( P < 0.05) inspiratory flow by 18.4 and 30.1%, respectively, where 80% CO2 also increased ( P < 0.05) tidal volume, heart rate, CO2 production, and O2 consumption. FA with 80% CO2 at multiple raphe sites also led to hyperventilation (−2 mmHg), indicating that FA had effects on breathing independent of an increased metabolic rate. We believe these findings suggest that the large ventilatory response to a global respiratory brain acidosis reflects the cumulative effect of stimulation at widespread chemoreceptor sites rather than a large stimulation at a single site. Additionally, focal acidification of raphe chemoreceptors appears to activate an established thermogenic response needed to offset the increased heat loss associated with the CO2 hyperpnea.

337 Nitric oxide exhalation correlates with ventilatory response to the exercise in patients with heart disease

2003 ◽  
Vol 2 (1) ◽  
pp. 63-64
Author(s):  
H ADACHI ◽  
S SAKURAI ◽  
T TOYAMA ◽  
H HOSHIZAKI ◽  
S OSHIMA ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Disease ◽  
Ventilatory Response
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