Targeting autonomic imbalance in pathophysiology: is the carotid body the new nirvana?

Paton, Julian F. R.

doi:10.1113/jp273604

Cited by 4 publications

(5 citation statements)

References 4 publications

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“…Although our study has focused on alterations in peripheral chemosensitivity, we cannot exclude a potential role of central chemoreceptors in increasing the sympathetic tone through the stimulation of carbon dioxide-sensitive neurons of the retrotrapezoid body [35]. However, the patients evaluated in our study did not present hypercapnia and, except for a slight nocturnal increase in arterial carbon dioxide tension (PaCO 2 ) in the INH group, did not show relevant changes in PaCO 2 .…”

Section: Discussionmentioning

confidence: 75%

The effect of treatment for sleep apnoea on determinants of blood pressure control

et al. 2017

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Our aim was to assess the effect of continuous positive airway pressure (CPAP) on the nocturnal evolution of peripheral chemosensitivity, renin-angiotensin-aldosterone system activity, sympathetic tone and endothelial biomarkers in obstructive sleep apnoea (OSA) patients with isolated nocturnal hypertension (INH) or day-night sustained hypertension (D-NSH).In a crossover randomised trial, 32 OSA patients newly diagnosed with hypertension and without antihypertensive treatment were randomly assigned to 12 weeks of CPAP or sham CPAP. Peripheral chemosensitivity was evaluated before and after sleep using the hypoxic withdrawal test (%Δ).At baseline, D-NSH patients showed higher %Δ before sleep and higher levels of aldosterone and diurnal catecholamines. CPAP only reduced the nocturnal increase of %Δ in INH patients (6.9%, 95% CI 1.0-12.8%; p=0.026). CPAP-induced change from baseline in %Δ after sleep was 7.5% (95% CI 2.6-12.2%, p=0.005) in the INH group and 5.7% (95% CI 2.2-9.3%, p=0.004) in the D-NSH group. In contrast, %Δ before sleep only decreased with CPAP in the D-NSH patients (3.0%, 95% CI 0.5-5.6%; p=0.023).In conclusion, CPAP reduces the nocturnal increase of peripheral chemosensitivity experienced by INH patients and corrects the high daytime sensitivity of patients with D-NSH. Differences in response to CPAP between these patients can help better understand the mechanisms of perpetuation of hypertension in sleep apnoea.

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Section: Discussionmentioning

confidence: 75%

The effect of treatment for sleep apnoea on determinants of blood pressure control

et al. 2017

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“…; Del Rio et al . ; Paton, ). For example, astrocyte transporter control of hypothalamic neurons is altered in heart failure (Potapenko et al .…”

Section: Discussionmentioning

confidence: 98%

“…Whether EAAT2 influences other reflex responses was not examined. Astrocyte modulation of glutamate signalling and tempered chemoreflex function may have substantial functional significance because elevated sympathetic nervous system activity and enhanced chemoreflexes are highly associated with morbidity and mortality in several cardiorespiratory diseases (Fisher et al 2009;Andrade et al 2015;Del Rio et al 2015;Paton, 2017). For example, astrocyte transporter control of hypothalamic neurons is altered in heart failure (Potapenko et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Glial EAAT2 regulation of extracellular nTS glutamate critically controls neuronal activity and cardiorespiratory reflexes

Matott

Kline

Hasser

2017

The Journal of Physiology

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Glutamatergic signalling is critical in the nucleus tractus solitarii (nTS) for cardiorespiratory homeostasis and initiation of sensory reflexes, including the chemoreflex activated during hypoxia. Maintenance of nTS glutamate concentration occurs in part through astrocytic excitatory amino acid transporters (EAATs). We previously established the importance of EAATs in the nTS by demonstrating their inhibition produced neuronal excitation to alter basal cardiorespiratory function. Since EAAT2 is the most expressed EAAT in the nTS, this study specifically determined EAAT2's role in nTS astrocytes, its influence on neuronal and synaptic properties, and ultimately on basal and reflex cardiorespiratory function. The EAAT2-specific antagonist dihydrokainate (DHK) was microinjected into the anaesthetized rat nTS or applied to rat nTS slices. DHK produced depressor, bradycardic and sympathoinhibitory responses and reduced neural respiration in the intact rat, mimicking responses to glutamate excitation. DHK also enhanced responses to glutamate microinjection. DHK elevated extracellular nTS glutamate concentration, depolarized neurons and enhanced spontaneous EPSCs. EAAT2 block also augmented action potential discharge in chemosensitive nTS neurons. Glial recordings confirmed EAAT2 is functional on nTS astrocytes. Neuronal excitation and cardiorespiratory effects following EAAT2 inhibition were due to activation of putative extrasynaptic AMPA receptors as their antagonism blocked DHK responses in the intact rat nTS and the slice. The DHK-induced elevation of extracellular glutamate and neuronal excitation augmented chemoreflex-mediated pressor, sympathoexcitatory and minute neural ventilation responses in the rat. These data shed new light on the important role astrocytic EAAT2 plays on buffering nTS excitation and overall cardiorespiratory function.

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“…Российский кардиологический журнал 2022; 27 (9) и ожирение ассоциированы с хроническим субклиническим воспалением, повышением концентрации продуктов окисления и инсулина, которые вызывают гиперстимуляцию каротидных телец. Сигнал от каротидных телец приводит к активации СНС и запуску механизмов развития АГ, а также инсулинорезистентности [17,18].…”

Section: артериальная гипертензияunclassified

Influence on the autonomic cardiovascular system regulation in the treatment of hypertension, arrhythmias and heart failure

et al. 2022

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Cardiovascular diseases are widespread and are the leading death cause in most countries, despite the creation and improvement of strategies to reduce cardiovascular risk. A significant role in the development and evolution of cardiovascular diseases belongs to sympathetic nervous system hyperactivity, and therefore the methods of effecting it are relevant for the prevention and treatment of cardiovascular pathology. The article discusses modern approaches to interventional and conservative regulation of the autonomic nervous system and neuromodulation in the prevention and treatment of hypertension, heart failure, tachyarrhythmias, as well as reflects a conjoint expert judgment on these issues.

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Targeting autonomic imbalance in pathophysiology: is the carotid body the new nirvana?

Cited by 4 publications

References 4 publications

The effect of treatment for sleep apnoea on determinants of blood pressure control

The effect of treatment for sleep apnoea on determinants of blood pressure control

Glial EAAT2 regulation of extracellular nTS glutamate critically controls neuronal activity and cardiorespiratory reflexes

Influence on the autonomic cardiovascular system regulation in the treatment of hypertension, arrhythmias and heart failure

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