Sympathetic dysregulation induced by postnatal intermittent hypoxia

Karlen‐Amarante, Marlusa; Leirão, Isabela de Paula; Katayama, Pedro L.; Colombari, Eduardo; Bittencourt-Silva, Paloma Graziele; Menezes, Miguel Ângelo; Zoccal, Daniel B.

doi:10.1093/sleep/zsad055

Cited by 7 publications

(12 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neurons in the NTS relay information to the hypothalamic paraventricular nucleus and sympathoexcitatory neurons in the RVLM (Herman & Cullinan, 1997;Sawchenko et al, 1996). A recent study reported that IH increases RVLM neuronal activity linked to presympathetic neurons (Karlen-Amarante et al, 2023). On the one hand, Zoccal et al (2011) believe that IH enhances purinergic but not glutamatergic transmission in the RVLM.…”

Section: Effect Of Ih On the Central Component Of The Carotid Body Ch...mentioning

confidence: 99%

Carotid body hypersensitivity in intermittent hypoxia and obtructive sleep apnoea

Prabhakar

Peng

Nanduri

2023

The Journal of Physiology

View full text Add to dashboard Cite

Carotid bodies are the principal sensory organs for detecting changes in arterial blood oxygen concentration, and the carotid body chemoreflex is a major regulator of the sympathetic tone, blood pressure and breathing. Intermittent hypoxia is a hallmark manifestation of obstructive sleep apnoea (OSA), which is a widespread respiratory disorder. In the first part of this review, we discuss the role of carotid bodies in heightened sympathetic tone and hypertension in rodents treated with intermittent hypoxia, and the underlying cellular, molecular and epigenetic mechanisms. We also present evidence for hitherto‐uncharacterized role of carotid body afferents in triggering cellular and molecular changes induced by intermittent hypoxia. In the second part of the review, we present evidence for a contribution of a hypersensitive carotid body to OSA and potential therapeutic intervention to mitigate OSA in a murine model. image

show abstract

Section: Effect Of Ih On the Central Component Of The Carotid Body Ch...mentioning

confidence: 99%

Carotid body hypersensitivity in intermittent hypoxia and obtructive sleep apnoea

Prabhakar

Peng

Nanduri

2023

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…While animal models cannot fully recapitulate the complexity of the clinical scenario, CIH models do produce an injury profile similar to that seen in humans, with respect to white matter loss, neurodevelopmental delay, and functional deficits [[11], [13]]. Very recently, it has been suggested that postnatal CIH might be a risk factor for developing cardiorespiratory diseases in adulthood as well [[64]]. The models generally involve several daily sessions of intermittent hypoxia over various days [[65]].…”

Section: Consequences Of Cih On Cerebrovascular Structure and Functionmentioning

confidence: 99%

Does Perinatal Intermittent Hypoxia Affect Cerebrovascular Network Development?

Coelho-Santos¹,

Cruz²,

Shih³

2023

Dev Neurosci

View full text Add to dashboard Cite

Perinatal hypoxia is an inadequate delivery of oxygen to the fetus in the period immediately before, during, or after the birth process. The most frequent form of hypoxia occurring in human development is chronic intermittent hypoxia (CIH) due to sleep-disordered breathing (apnea) or bradycardia events. CIH incidence is particularly high with premature infants. During CIH, repetitive cycles of hypoxia and reoxygenation initiate oxidative stress and inflammatory cascades in the brain. A dense microvascular network of arterioles, capillaries, and venules is required to support the constant metabolic demands of the adult brain. The development and refinement of this microvasculature is orchestrated throughout gestation and in the initial weeks after birth, at a critical juncture when CIH can occur. There is little knowledge on how CIH affects the development of the cerebrovasculature. However, since CIH (and its treatments) can cause profound abnormalities in tissue oxygen content and neural activity, there is reason to believe that it can induce lasting abnormalities in vascular structure and function at the microvascular level contributing to neurodevelopmental disorders. This mini-review discusses the hypothesis that CIH induces a positive feedback loop to perpetuate metabolic insufficiency through derailment of normal cerebrovascular development, leading to long-term deficiencies in cerebrovascular function.

show abstract

“…In rats, CIH increases sympathetic activity and disrupts respiratory-sympathetic coupling resulting in hypertension ( Zoccal et al, 2008 ; Simms et al, 2009 ; Zoccal et al, 2009 ; Molkov et al, 2011 ). Furthermore, when exposure to CIH occurs postnatally, elevated arterial pressure levels and baroreflex dysfunctions can persist into adulthood ( Soukhova-O'Hare et al, 2006 ; Karlen-Amarante et al, 2023 ). The cardiopulmonary effects of CIH have been attributed to the overexcitation of rostral ventrolateral medulla (RVLM) presympathetic neurons ( Karlen-Amarante et al, 2023 ) via excitatory and inhibitory inputs from respiratory rhythmogenic networks ( Lipski et al, 1996 ; Molkov et al, 2011 ; Moraes et al, 2012 , 2013 ).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, when exposure to CIH occurs postnatally, elevated arterial pressure levels and baroreflex dysfunctions can persist into adulthood ( Soukhova-O'Hare et al, 2006 ; Karlen-Amarante et al, 2023 ). The cardiopulmonary effects of CIH have been attributed to the overexcitation of rostral ventrolateral medulla (RVLM) presympathetic neurons ( Karlen-Amarante et al, 2023 ) via excitatory and inhibitory inputs from respiratory rhythmogenic networks ( Lipski et al, 1996 ; Molkov et al, 2011 ; Moraes et al, 2012 , 2013 ). However, the exact neuronal mechanisms underlying respiratory modulation of sympathetic activity remain to be characterized.…”

Section: Introductionmentioning

confidence: 99%

Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia

Karlen-Amarante,

Glovak,

Huff

et al. 2024

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

The sympathetic nervous system modulates arterial blood pressure. Individuals with obstructive sleep apnea (OSA) experience numerous nightly hypoxic episodes and exhibit elevated sympathetic activity to the cardiovascular system leading to hypertension. This suggests that OSA disrupts normal respiratory-sympathetic coupling. This study investigates the role of the postinspiratory complex (PiCo) and preBötzinger complex (preBötC) in respiratory-sympathetic coupling under control conditions and following exposure to chronic intermittent hypoxia (CIH) for 21 days (5% O2–80 bouts/day). The surface of the ventral brainstem was exposed in urethane (1.5 g/kg) anesthetized, spontaneously breathing adult mice. Cholinergic (ChAT), glutamatergic (Vglut2), and neurons that co-express ChAT and Vglut2 at PiCo, as well as Dbx1 and Vglut2 neurons at preBötC, were optogenetically stimulated while recording activity from the diaphragm (DIA), vagus nerve (cVN), and cervical sympathetic nerve (cSN). Following CIH exposure, baseline cSN activity increased, breathing frequency increased, and expiratory time decreased. In control mice, stimulating PiCo specific cholinergic-glutamatergic neurons caused a sympathetic burst during all phases of the respiratory cycle, whereas optogenetic activation of cholinergic-glutamatergic PiCo neurons in CIH mice increased sympathetic activity only during postinspiration and late expiration. Stimulation of glutamatergic PiCo neurons increased cSN activity during the postinspiratory phase in control and CIH mice. Optogenetic stimulation of ChAT containing neurons in the PiCo area did not affect sympathetic activity under control or CIH conditions. Stimulating Dbx1 or Vglut2 neurons in preBötC evoked an inspiration and a concomitant cSN burst under control and CIH conditions. Taken together, these results suggest that PiCo and preBötC contribute to respiratory-sympathetic coupling, which is altered by CIH, and may contribute to the hypertension observed in patients with OSA.

show abstract

Sympathetic dysregulation induced by postnatal intermittent hypoxia

Cited by 7 publications

References 57 publications

Carotid body hypersensitivity in intermittent hypoxia and obtructive sleep apnoea

Carotid body hypersensitivity in intermittent hypoxia and obtructive sleep apnoea

Does Perinatal Intermittent Hypoxia Affect Cerebrovascular Network Development?

Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia

Contact Info

Product

Resources

About