Changes in the Carotid Body and the Ventilatory Response to Hypoxia in Chronically Hypoxic Rats

1976 ◽  
Vol 50 (4) ◽  
pp. 311-313 ◽  
Author(s):  
Gwenda R. Barer ◽  
C. W. Edwards ◽  
Angela I. Jolly
Keyword(s):  
High Altitude ◽  
Carotid Body ◽  
Ventilatory Response ◽  
Littermate Control ◽  
Young Rats ◽  
Carotid Bodies ◽  
Ventilatory Response To Hypoxia

1. Young rats were kept in a hypoxic chamber for 2–11 weeks and compared with littermate control animals. 2. The carotid bodies of the hypoxic rats enlarged, resembling those of men and animals living at high altitude. 3. Permanent blunting of the ventilatory response to hypoxia did not occur. Immediately on removal from the chamber, the rats, lightly anaesthetized, showed a smaller increase in ventilation during hypoxia than did control animals but this difference disappeared after 3 days' recovery in normoxia.

Dopamine and ventilatory effects of hypoxia and almitrine in chronically hypoxic rats

1989 ◽  
Vol 67 (1) ◽  
pp. 186-192 ◽  
Author(s):  
R. A. Wach ◽  
D. Bee ◽  
G. R. Barer
Keyword(s):  
Carotid Body ◽  
Ventilatory Response ◽  
Response Curves ◽  
Enhancing Effect ◽  
Stimulus Response ◽  
Ventilatory Responses ◽  
Carotid Bodies ◽  
Ventilatory Effects ◽  
Ventilatory Response To Hypoxia

We hypothesized that the temporary blunted ventilatory response to hypoxia seen in chronically hypoxic rats could be related to the increased amount of dopamine found in their carotid bodies. Rats, kept 2–3 wk in 10% O2, showed reduced nonisocapnic ventilatory responses to 21–12% inspiratory O2 fraction compared with control rats. Stimulus-response curves to almitrine, which simulates the action of hypoxia on the carotid body, were also depressed in chronically hypoxic rats. Responses to hypoxia and almitrine were significantly correlated in the two groups of rats. Dopamine depressed ventilation during normoxia, hypoxia, and almitrine stimulation in both groups, an action abolished by the dopamine-2 antagonist domperidone. Domperidone slightly increased responses to hypoxia and almitrine in control rats but had a greater enhancing effect in chronically hypoxic rats, such that there was no longer a difference between the responses of the two groups.

Intermittent hypoxia augments carotid body and ventilatory response to hypoxia in neonatal rat pups

2004 ◽  
Vol 97 (5) ◽  
pp. 2020-2025 ◽  
Author(s):  
Ying-Jie Peng ◽  
Julie Rennison ◽  
Nanduri R. Prabhakar
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Time Course ◽  
Ventilatory Response ◽  
Neonatal Rat ◽  
Sensory Response ◽  
Rat Pups ◽  
Carotid Bodies ◽  
And Control ◽  
Ventilatory Response To Hypoxia

Carotid bodies are functionally immature at birth and exhibit poor sensitivity to hypoxia. Previous studies have shown that continuous hypoxia at birth impairs hypoxic sensing at the carotid body. Intermittent hypoxia (IH) is more frequently experienced in neonatal life. Previous studies on adult animals have shown that IH facilitates hypoxic sensing at the carotid bodies. On the basis of these studies, in the present study we tested the hypothesis that neonatal IH facilitates hypoxic sensing of the carotid body and augments ventilatory response to hypoxia. Experiments were performed on 2-day-old rat pups that were exposed to 16 h of IH soon after the birth. The IH paradigm consisted of 15 s of 5% O2 (nadir) followed by 5 min of 21% O2 (9 episodes/h). In one group of experiments (IH and control, n = 6 pups each), sensory activity was recorded from ex vivo carotid bodies, and in the other (IH and control, n = 7 pups each) ventilation was monitored in unanesthetized pups by plethysmography. In control pups, sensory response of the carotid body was weak and was slow in onset (∼100 s). In contrast, carotid body sensory response to hypoxia was greater and the time course of the response was faster (∼30 s) in IH compared with control pups. The magnitude of the hypoxic ventilatory response was greater in IH compared with control pups, whereas changes in O2 consumption and CO2 production during hypoxia were comparable between both groups. The magnitude of ventilatory stimulation by hyperoxic hypercapnia (7% CO2-balance O2), however, was the same between both groups of pups. These results demonstrate that neonatal IH facilitates carotid body sensory response to hypoxia and augments hypoxic ventilatory chemoreflex.

scholarly journals Ventilatory Response to Hypoxia during Endotoxemia in Young Rats: Role of Nitric Oxide

2007 ◽  
Vol 62 (2) ◽  
pp. 134-138 ◽  
Author(s):  
John Ladino ◽  
Eduardo Bancalari ◽  
Cleide Suguihara
Keyword(s):  
Nitric Oxide ◽  
Ventilatory Response ◽  
Young Rats ◽  
Ventilatory Response To Hypoxia

scholarly journals The hypoxic ventilatory response is facilitated by the activation of Lkb1-AMPK signalling pathways downstream of the carotid bodies

2019 ◽  
Author(s):  
Amira D. Mahmoud ◽  
Andrew P. Holmes ◽  
Sandy MacMillan ◽  
Oluseye A. Ogunbayo ◽  
Christopher N. Wyatt ◽  
...  
Keyword(s):  
Carotid Body ◽  
Ventilatory Response ◽  
Afferent Input ◽  
The Body ◽  
System Level ◽  
Type I ◽  
Hypoxic Ventilatory Response ◽  
Level Control ◽  
Body Type ◽  
Carotid Bodies

ABSTRACTWe recently demonstrated that the role of the AMP-activated protein kinase (AMPK), a ubiquitously expressed enzyme that governs cell-autonomous metabolic homeostasis, has been extended to system-level control of breathing and thus oxygen and energy (ATP) supply to the body. Here we assess the contribution to the hypoxic ventilatory response (HVR) of two upstream kinases that govern the activities of AMPK. Lkb1, which activates AMPK in response to metabolic stress and CaMKK2 which mediates the alternative Ca2+-dependent mechanism of AMPK activation. HVRs remained unaffected in mice with global deletion of the CaMKK2 gene. By contrast, HVRs were markedly attenuated in mice with conditional deletion of LKB1 in catecholaminergic cells, including carotid body type I cells and brainstem respiratory networks. In these mice hypoxia evoked hypoventilation, apnoea and Cheyne-Stokes-like breathing, rather than hyperventilation. Attenuation of HVRs, albeit less severe, was also conferred in mice carrying ∼90% knockdown of Lkb1 expression. Carotid body afferent input responses were retained following either ∼90% knockdown of Lkb1 or AMPK deletion. In marked contrast, LKB1 deletion virtually abolished carotid body afferent discharge during normoxia, hypoxia and hypercapnia. We conclude that Lkb1 and AMPK, but not CaMKK2, facilitate HVRs at a site downstream of the carotid bodies.

Effects of carotid body hypocapnia during ventilatory acclimatization to hypoxia

1997 ◽  
Vol 82 (1) ◽  
pp. 118-124 ◽  
Author(s):  
M. R. Dwinell ◽  
P. L. Janssen ◽  
J. Pizarro ◽  
G. E. Bisgard
Keyword(s):  
Carotid Body ◽  
Ventilatory Response ◽  
Control Level ◽  
Blood Gases ◽  
Initial Response ◽  
Time Dependent ◽  
Hypoxic Exposure ◽  
Dependent Manner ◽  
Additional Group ◽  
Ventilatory Response To Hypoxia

Dwinell, M. R., P. L. Janssen, J. Pizarro, and G. E. Bisgard. Effects of carotid body hypocapnia during ventilatory acclimatization to hypoxia. J. Appl. Physiol. 82(1): 118–124, 1997.—Hypoxic ventilatory sensitivity is increased during ventilatory acclimatization to hypoxia (VAH) in awake goats, resulting in a time-dependent increase in expired ventilation (V˙e). The objectives of this study were to determine whether the increased carotid body (CB) hypoxic sensitivity is dependent on the level of CB CO2 and whether the CB CO2 gain is changed during VAH. Studies were carried out in adult goats with CB blood gases controlled by an extracorporeal circuit while systemic (central nervous system) blood gases were regulated independently by the level of inhaled gases. Acute V˙e responses to CB hypoxia (CB [Formula: see text] 40 Torr) and CB hypercapnia (CB [Formula: see text] 50 and 60 Torr) were measured while systemic normoxia and isocapnia were maintained. CB[Formula: see text] was then lowered to 40 Torr for 4 h while the systemic blood gases were kept normoxic and normocapnic. During the 4-h CB hypoxia, V˙e increased in a time-dependent manner. Thirty minutes after return to normoxia, the ventilatory response to CB hypoxia was significantly increased compared with the initial response. The slope of the CB CO2 response was also elevated after VAH. An additional group of goats ( n = 7) was studied with a similar protocol, except that CB [Formula: see text]was lowered throughout the 4-h hypoxic exposure to prevent reflex hyperventilation. CB [Formula: see text] was progressively lowered throughout the 4-h CB hypoxic period to maintainV˙e at the control level. After the 4-h CB hypoxic exposure, the ventilatory response to hypoxia was also significantly elevated. However, the slope of the CB CO2 response was not elevated after the 4-h hypoxic exposure. These results suggest that CB sensitivity to both O2 and CO2 is increased after 4 h of CB hypoxia with systemic isocapnia. The increase in CB hypoxic sensitivity is not dependent on the level of CB CO2 maintained during the 4-h hypoxic period.

Influence of pregnancy on ventilatory and carotid body neural output responsiveness to hypoxia in cats

1989 ◽  
Vol 67 (2) ◽  
pp. 797-803 ◽  
Author(s):  
B. Hannhart ◽  
C. K. Pickett ◽  
J. V. Weil ◽  
L. G. Moore
Keyword(s):  
Carotid Body ◽  
Ventilatory Response ◽  
Hypoxic Ventilatory Response ◽  
Air Ventilation ◽  
Near Term ◽  
End Tidal ◽  
Neural Influences ◽  
End Tidal Co2 ◽  
Ventilatory Response To Hypoxia

Pregnancy increases ventilation and ventilatory sensitivity to hypoxia and hypercapnia. To determine the role of the carotid body in the increased hypoxic ventilatory response, we measured ventilation and carotid body neural output (CBNO) during progressive isocapnic hypoxia in 15 anesthetized near-term pregnant cats and 15 nonpregnant females. The pregnant compared with nonpregnant cats had greater room-air ventilation [1.48 +/- 0.24 vs. 0.45 +/- 0.05 (SE) l/min BTPS, P less than 0.01], O2 consumption (29 +/- 2 vs. 19 +/- 1 ml/min STPD, P less than 0.01), and lower end-tidal PCO2 (30 +/- 1 vs. 35 +/- 1 Torr, P less than 0.01). Lower end-tidal CO2 tensions were also observed in seven awake pregnant compared with seven awake nonpregnant cats (28 +/- 1 vs. 31 +/- 1 Torr, P less than 0.05). The ventilatory response to hypoxia as measured by the shape of parameter A was twofold greater (38 +/- 5 vs. 17 +/- 3, P less than 0.01) in the anesthetized pregnant compared with nonpregnant cats, and the CBNO response to hypoxia was also increased twofold (58 +/- 11 vs. 29 +/- 5, P less than 0.05). The increased CBNO response to hypoxia in the pregnant compared with the nonpregnant cats persisted after cutting the carotid sinus nerve while recording from the distal end, indicating that the increased hypoxic sensitivity was not due to descending central neural influences. We concluded that greater carotid body sensitivity to hypoxia contributed to the increased hypoxic ventilatory responsiveness observed in pregnant cats.

Interindividual variation in hypoxic ventilatory response: potential role of carotid body

1987 ◽  
Vol 63 (5) ◽  
pp. 1884-1889 ◽  
Author(s):  
M. Vizek ◽  
C. K. Pickett ◽  
J. V. Weil
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Interindividual Variation ◽  
Potential Contribution ◽  
Hypoxic Ventilatory Response ◽  
Peripheral Chemoreceptor ◽  
Interindividual Differences ◽  
Carotid Bodies ◽  
Considerable Interindividual Variation ◽  
Ventilatory Response To Hypoxia

There is considerable interindividual variation in ventilatory response to hypoxia in humans but the mechanism remains unknown. To examine the potential contribution of variable peripheral chemorecptor function to variation in hypoxic ventilatory response (HVR), we compared the peripheral chemoreceptor and ventilatory response to hypoxia in 51 anesthetized cats. We found large interindividual differences in HVR spanning a sevenfold range. In 23 cats studied on two separate days, ventilatory measurements were correlated (r = 0.54, P less than 0.01), suggesting stable interindividual differences. Measurements during wakefulness and in anesthesia in nine cats showed that although anesthesia lowered the absolute HVR it had no influence on the range or the rank of the magnitude of the response of individuals in the group. We observed a positive correlation between ventilatory and carotid sinus nerve (CSN) responses to hypoxia measured during anesthesia in 51 cats (r = 0.63, P less than 0.001). To assess the translation of peripheral chemoreceptor activity into expiratory minute ventilation (VE) we used an index relating the increase of VE to the increase of CSN activity for a given hypoxic stimulus (delta VE/delta CSN). Comparison of this index for cats with lowest (n = 5, HVR A = 7.0 +/- 0.8) and cats with highest (n = 5, HVR A = 53.2 +/- 4.9) ventilatory responses showed similar efficiency of central translation (0.72 +/- 0.06 and 0.70 +/- 0.08, respectively). These results indicate that interindividual variation in HVR is associated with comparable variation in hypoxic sensitivity of carotid bodies. Thus differences in peripheral chemoreceptor sensitivity may contribute to interindividual variability of HVR.

scholarly journals Activation of Opioid μ-Receptors in the Commissural Subdivision of the Nucleus Tractus Solitarius Abolishes the Ventilatory Response to Hypoxia in Anesthetized Rats

2011 ◽  
Vol 115 (2) ◽  
pp. 353-363 ◽  
Author(s):  
Zhenxiong Zhang ◽  
Jianguo Zhuang ◽  
Cancan Zhang ◽  
Fadi Xu
Keyword(s):  
Carotid Body ◽  
Nucleus Tractus Solitarius ◽  
Ventilatory Response ◽  
Hypercapnic Ventilatory Response ◽  
Study Results ◽  
Spontaneously Breathing ◽  
Similar Decrease ◽  
Ventilatory Response To Hypoxia ◽  
Μ Receptor ◽  
Carotid Body Denervation

Background : The commissural subnucleus of the nucleus tractus solitarius (comNTS) is a key region in the brainstem responsible for the hypoxic ventilatory response (HVR) because it contains the input terminals of the carotid chemoreceptor. Because opioids inhibit the HVR via activating central μ-receptors that are expressed abundantly in the comNTS, the authors of the current study asked whether activating local μ-receptors attenuated the carotid body-mediated HVR. Methods : To primarily stimulate the carotid body, brief hypoxia (100% N2) and hypercapnia (15% CO2) for 10 s and/or intracarotid injection of NaCN (10 μg/100 μl) were performed in anesthetized and spontaneously breathing rats. These stimulations were repeated after: (1) microinjecting three doses of μ-receptor agonist [d-Ala2, N-Me-Phe4, Gly-ol]-Enkephalin (DAMGO) (approximately 3.5 nl) into the comNTS; (2) carotid body denervation; and (3) systemic administration of DAMGO (300 μg/kg) without and with previous intracomNTS injection of d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2, a μ-receptor antagonist. Results : Study results showed that DAMGO at 0.25 and 2.5, but not 0.025 mM, caused a similar decrease in baseline ventilation (approximately 12%). DAMGO at 0.25 mM largely reduced (64%) the HVR, whereas DAMGO at 2.5 mM abolished the HVR (and the VE response to NaCN) and moderately attenuated (31%) the hypercapnic ventilatory response. Interestingly, similar HVR abolition and depression of the hypercapnic ventilatory response were observed after carotid body denervation. Blocking comNTS μ-receptors by d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 significantly attenuated the HVR depression by systemic DAMGO with little change in the DAMGO modulatory effects on baseline ventilation and the hypercapnic ventilatory response. Conclusion : The data suggest that opioids within the comNTS, via acting on μ-receptors, are able to abolish the HVR by affecting the afferent pathway of the carotid chemoreceptor.

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