engleski

Serotonergic modulation of hypercapnia induced respiratory plasticity – changes in phrenic nerve activity

Intermittent hypercapnia, along with hypoxia, is a concomitant feature seen in obstructive sleep apnea patients. Intermittent hypercapnia can evoke long-term depression of phrenic nerve activity, but inconsistency in its manifestation, indicates involvement of additional factors. This study was performed to investigate effects of episodic hypercapnia, and the role of intravenous injection of 5-HT receptors antagonist methysergide on phrenic nerve activity after exposures to intermittent hypercapnic stimulus. Twelve, male, urethane anesthetized, vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats, were exposed to the acute intermittent hypercapnia (HC) protocol. Protocol consisted of 5 hypercapnic episodes (15% CO2), each lasting for 3 min (HC, control group, N=7). Experimental group (MeHC group, N=5) received an intravenous injection of methysergide, before the onset of the first hypercapnia. Peak phrenic nerve activity (pPNA), burst frequency, and breathing rhythm parameters were analyzed during the first hypercapnia, at 15, 30, and 60 minutes after the end of the last hypercapnia, and compared to the baseline values. In control group, non-significant changes of the pPNA were observed 15, 30 and 60 minutes after the last hypercapnia (pPNA was 107.3±16.6%, 84.1±21.0% and 92.5±18.5%, respectively, p=1.00). In MeHC group, significant decrease of pPNA 15, 30 and 60 min after the last hypercapnia was observed (64.1±5.0%, 57.9±6.8% and 49.6±6.7%, respectively, p<0.05), compared to baseline. Administration of methysergide prior to the onset of the hypercapnia protocol intensified depression of the phrenic nerve activity following intermittent hypercapnia exposure.

serotonin; hypercapnia; respiratory plasticity; phrenic nerve

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