Acute intermittent hypoxia with concurrent hypercapnia evokes P2X and TRPV1 receptor‐dependent sensory long‐term facilitation in naïve carotid bodies
Notice bibliographique
Résumé
Key points Activity‐dependent plasticity can be induced in carotid body (CB) chemosensory afferents without chronic intermittent hypoxia (CIH) preconditioning by acute intermittent hypoxia coincident with bouts of hypercapnia (AIH‐Hc). Several properties of this acute plasticity are shared with CIH‐dependent sensory long‐term facilitation (LTF) in that induction is dependent on 5‐HT, angiotensin II, protein kinase C and reactive oxygen species. Several properties differ from CIH‐dependent sensory LTF; H2O2 appears to play no part in induction, whereas maintenance requires purinergic P2X2/3 receptor activation and is dependent on transient receptor potential vanilloid type 1 (TRPV1) receptor sensitization. Because P2X2/3 and TRPV1 receptors are located in carotid sinus nerve (CSN) terminals but not presynaptic glomus cells, a primary site of the acute AIH‐Hc induced sensory LTF appears to be postsynaptic. Our results obtained in vivo suggest a role for TRPV1‐dependent CB activity in acute sympathetic LTF. We propose that P2X‐TRPV1‐receptor‐dependent sensory LTF may constitute an important early mechanism linking sleep apnoea with hypertension and/or cardiovascular disease. Abstract Apnoeas constitute an acute existential threat to neonates and adults. In large part, this threat is detected by the carotid bodies, which are the primary peripheral chemoreceptors, and is combatted by arousal and acute cardiorespiratory responses, including increased sympathetic output. Similar responses occur with repeated apnoeas but they continue beyond the last apnoea and can persist for hours [i.e. ventilatory and sympathetic long‐term facilitation (LTF)]. These long‐term effects may be adaptive during acute episodic apnoea, although they may prolong hypertension causing chronic cardiovascular impairment. We report a novel mechanism of acute carotid body (CB) plasticity (sensory LTF) induced by repeated apnoea‐like stimuli [i.e. acute intermittent hypoxia coincident with bouts of hypercapnia (AIH‐Hc)]. This plasticity did not require chronic intermittent hypoxia preconditioning, was dependent on P2X receptors and protein kinase C, and involved heat‐sensitive transient receptor potential vanilloid type 1 (TRPV1) receptors. Reactive oxygen species (O2·¯) were involved in initiating plasticity only; no evidence was found for H2O2 involvement. Angiotensin II and 5‐HT receptor antagonists, losartan and ketanserin, severely reduced CB responses to individual hypoxic‐hypercapnic challenges and prevented the induction of sensory LTF but, if applied after AIH‐Hc, failed to reduce plasticity‐associated activity. Conversely, TRPV1 receptor antagonism had no effect on responses to individual hypoxic‐hypercapnic challenges but reduced plasticity‐associated activity by ∼50%. Further, TRPV1 receptor antagonism in vivo reduced sympathetic LTF caused by AIH‐Hc, although only if the CBs were functional. These data demonstrate a new mechanism of CB plasticity and suggest P2X‐TRPV1‐dependent sensory LTF as a novel target for pharmacological intervention in some forms of neurogenic hypertension associated with recurrent apnoeas.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».