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.

Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity

2004 ◽  
Vol 96 (3) ◽  
pp. 1236-1242 ◽  
Author(s):  
Ying-Jie Peng ◽  
Nanduri R. Prabhakar
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Ex Vivo ◽  
Previous Treatment ◽  
Male Rats ◽  
Sensory Response ◽  
Chronic Intermittent Hypoxia ◽  
Radical Scavenger ◽  
Sprague Dawley ◽  
Carotid Bodies

Reflexes arising from the carotid bodies may play an important role in cardiorespiratory changes evoked by chronic intermittent hypoxia (CIH). In the present study, we examined whether CIH affects the hypoxic sensing ability of the carotid bodies and, if so, by what mechanisms. Experiments were performed on adult male rats (Sprague-Dawley, 250–300 g) exposed to two paradigms of CIH for 10 days: 1) multiple exposures to short durations of intermittent hypoxia per day (SDIH; 15sof5%O2 + 5 min of 21% O2, 9 episodes/h, 8 h/day) and 2) single exposure to longer durations of intermittent hypoxia per day [LDIH; 4 h of hypobaric hypoxia (0.4 atm/day) + 20 h of normoxia]. Carotid body sensory response to graded isocapnic hypoxia was examined in both groups of animals under anesthetized conditions. Hypoxic sensory response was significantly enhanced in SDIH but not in LDIH animals. Similar enhancement in hypoxic sensory response was also elicited in ex vivo carotid bodies from SDIH animals, suggesting that the effects were not secondary to cardiovascular changes. SDIH, however, had no significant effect on the hypercapnic sensory response. The effects of SDIH on the hypoxic sensory response completely reversed after SDIH animals were placed in a normoxic environment for an additional 10 days. Previous treatment with systemic administration of [Formula: see text] radical scavenger prevented SDIH-induced augmentation of the hypoxic sensory response. These results demonstrate that SDIH but not LDIH results in selective augmentation of the hypoxic response of the carotid body and [Formula: see text] radicals play an important role in SDIH-induced sensitization of the carotid body.

scholarly journals Comparative analysis of neonatal and adult rat carotid body responses to chronic intermittent hypoxia

2008 ◽  
Vol 104 (5) ◽  
pp. 1287-1294 ◽  
Author(s):  
Anita Pawar ◽  
Ying-Jie Peng ◽  
Frank J. Jacono ◽  
Nanduri R. Prabhakar
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Ex Vivo ◽  
Adult Life ◽  
Sensory Response ◽  
Chronic Intermittent Hypoxia ◽  
Adult Rats ◽  
Adult Rat ◽  
Carotid Bodies

Previous studies suggest that carotid body responses to long-term changes in environmental oxygen differ between neonates and adults. In the present study we tested the hypothesis that the effects of chronic intermittent hypoxia (CIH) on the carotid body differ between neonates and adult rats. Experiments were performed on neonatal (1–10 days) and adult (6–8 wk) males exposed either to CIH (9 episodes/h; 8 h/day) or to normoxia. Sensory activity was recorded from ex vivo carotid bodies. CIH augmented the hypoxic sensory response (HSR) in both groups. The magnitude of CIH-evoked hypoxic sensitization was significantly greater in neonates than in adults. Seventy-two episodes of CIH were sufficient to evoke hypoxic sensitization in neonates, whereas as many as 720 CIH episodes were required in adults, suggesting that neonatal carotid bodies are more sensitive to CIH than adult carotid bodies. CIH-induced hypoxic sensitization was reversed in adult rats after reexposure to 10 days of normoxia, whereas the effects of neonatal CIH persisted into adult life (2 mo). Acute intermittent hypoxia (IH) evoked sensory long-term facilitation of the carotid body activity (sensory LTF, i.e., increased baseline neural activity following acute IH) in CIH-exposed adults but not in neonates. The effects of CIH were associated with hyperplasia of glomus cells in neonatal but not in adult carotid bodies. These observations demonstrate that responses to CIH differ between neonates and adults with regard to the magnitude of sensitization of HSR, susceptibility to CIH, induction of sensory LTF, reversibility of the responses, and morphological remodeling of the chemoreceptor tissue.

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.

scholarly journals Reactive oxygen species-dependent endothelin signaling is required for augmented hypoxic sensory response of the neonatal carotid body by intermittent hypoxia

2009 ◽  
Vol 296 (3) ◽  
pp. R735-R742 ◽  
Author(s):  
Anita Pawar ◽  
Jayasri Nanduri ◽  
Guoxiang Yuan ◽  
Shakil A. Khan ◽  
Ning Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Reactive Oxygen ◽  
Sensory Response ◽  
Oxygen Species ◽  
Glomus Cells ◽  
Receptor Mrna ◽  
Carotid Bodies ◽  
Basal Release

We previously reported that intermittent hypoxia (IH) augments hypoxic sensory response (HSR) and increases the number of glomus cells in neonatal carotid bodies. In the present study, we tested the hypothesis that recruitment of endothelin-1 (ET-1) signaling by reactive oxygen species (ROS) plays a critical role in IH-evoked changes in neonatal carotid bodies. Experiments were performed on neonatal rats exposed either to 10 days of IH (P0–P10; 8 h/day) or to normoxia. IH augmented HSR of the carotid bodies ex vivo and resulted in hyperplasia of glomus cells. The effects of IH were associated with enhanced basal release of ET-1 under normoxia, sensitization of carotid body response to exogenous ET-1, and upregulation of ETA but not an ETB receptor mRNA without altering the ET-1 content. An ETA but not ETB receptor antagonist prevented augmented HSR by IH. ROS levels were elevated in carotid bodies from IH-treated rat pups as evidenced by increased levels of malondialdehyde. Systemic administration of manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (MnTMPyP; 5 mg/kg ip), a scavenger of O2•−, prevented IH-induced elevation of ROS, basal release of ET-1, upregulation of ETA mRNA, and augmented HSR. In striking contrast, MnTMPyP treatment had no significant effect on IH-induced hyperplasia of glomus cells. These results demonstrate that IH-evoked increase in HSR involve a ROS-mediated increase in basal ET-1 release and upregulation of ETA receptor mRNA.

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.

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.

Effects of age on ACTH, corticosterone, glucose, insulin, and mRNA levels during intermittent hypoxia in the neonatal rat

2013 ◽  
Vol 304 (9) ◽  
pp. R782-R789 ◽  
Author(s):  
Kathan Chintamaneni ◽  
Eric D. Bruder ◽  
Hershel Raff
Keyword(s):  
Mrna Expression ◽  
Glucose Homeostasis ◽  
Intermittent Hypoxia ◽  
Neonatal Rat ◽  
Mrna Levels ◽  
Plasma Acth ◽  
Tissue Samples ◽  
Rat Pups ◽  
Developmental Age ◽  
Adrenal Response

Apnea, the temporary cessation of respiratory airflow, is a common cause of intermittent hypoxia (IH) in premature infants. We hypothesized that IH elicits a stress response and alters glucose homeostasis in the neonatal rat. Rat pups were studied on postnatal day (PD) 2, 8, 10, 12, and 14. Pups were exposed to normoxia (control) or six cycles consisting of 30-s exposures to hypoxia (FiO2 = 3%) over a 60-min period. Blood samples were obtained at baseline, after the third cycle (∼30 min), and after the sixth cycle (∼60 min). Tissue samples were collected following the sixth cycle. Plasma ACTH, corticosterone, glucose, and insulin were analyzed at all ages. Hypothalamic, pituitary, and adrenal mRNA expression was evaluated by quantitative PCR in PD2, PD8, and PD12 pups. Exposure to IH elicited significant increases in plasma ACTH and corticosterone at all ages studied. The largest increase in corticosterone occurred in PD2 pups, despite only a very small increase in plasma ACTH. This ACTH-independent increase in corticosterone in PD2 pups was associated with increases in adrenal Ldlr and Star mRNA expression. Additionally, IH caused hyperglycemia and hyperinsulinemia at all ages. We conclude that IH elicits a significant pituitary-adrenal response and significantly alters glucose homeostasis. Furthermore, the quantitative and qualitative characteristics of these responses depend on developmental age.

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