Intermittent Hypoxia-Induced Sensitization of Central Chemoreceptors Contributes to Sympathetic Nerve Activity during Late Expiration in Rats

YI Molkov, DB Zoccal, DJA Moraes, JFR Paton, BH Machado, IA Rybak

Research output: Contribution to journalArticle (Academic Journal)peer-review

72 Citations (Scopus)

Abstract

Hypertension elicited by chronic intermittent hypoxia (CIH) is associated with elevated activity of the thoracic sympathetic nerve (tSN) that exhibits an enhanced respiratory modulation reflecting a strengthened interaction between respiratory and sympathetic networks within the brainstem. Expiration is a passive process except for special metabolic conditions as hypercapnia when it becomes active through phasic excitation of abdominal motor nerves (AbN) in late expiration. An increase in CO(2) evokes late-expiratory (late-E) discharges phase-locked to phrenic bursts with the frequency increasing quantally as hypercapnia increases. In rats exposed to CIH, the late-E discharges synchronized in AbN and tSN emerge in normocapnia. To elucidate the possible neural mechanisms underlying these phenomena we extended our computational model of the brainstem respiratory network by incorporating a population of pre-sympathetic neurons in the rostral ventrolateral medulla that received inputs from the pons, medullary respiratory compartments and retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). Our simulations proposed that CIH-conditioning increases the CO(2) sensitivity of RTN/pFRG neurons causing a reduction in both the CO(2) threshold for emerging the late-E activity in AbN and tSN and the hypocapnic threshold for apnea. Using the in situ rat preparations we confirmed that CIH-conditioned rats under normal conditions exhibit synchronized late-E discharges in AbN and tSN similar to those observed in control rats during hypercapnia. Moreover, the hypocapnic threshold for apnea was significantly lowered in CIH-conditioned rats relative to control rats. We conclude that CIH may sensitize central chemoreception and this significantly contributes to the neural impetus for generation of sympathetic activity and hypertension.
Translated title of the contributionIntermittent Hypoxia-Induced Sensitization of Central Chemoreceptors Contributes to Sympathetic Nerve Activity during Late Expiration in Rats
Original languageEnglish
JournalJournal of Neurophysiology
DOIs
Publication statusPublished - 2011

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