engleski

Phrenic long-term depression evoked by intermittent hypercapnia is modulated by serotonergic and adrenergic receptors in raphe nuclei.

Intermittent hypercapnia evokes prolonged depression of phrenic nerve activity (phrenic long-term depression, pLTD). This study was undertaken to investigate the role of 5-HT and α2- adrenergic receptors in the initiation of pLTD. Adult, male, urethane-anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague- Dawley rats were exposed to the protocol of acute intermittent hypercapnia (5 episodes of 15% CO2 in air, each episode lasting 3 minutes). Experimental group received microinjection of selective 5-HT1A receptors agonist 8-OH-DPAT, broad spectrum 5-HT antagonist methysergide or α2-adrenergic antagonist yohimbine, whereas control group received microinjection of 0.9% saline into the caudal raphe region. Peak phrenic nerve activity (pPNA) and burst frequency (f) were analyzed during baseline (T0), five hypercapnic episodes (THc1-5) and at 15, 30, and 60 minutes after the end of the last hypercapnia. In the control group, pPNA decreased 60 minutes after the end of the last hypercapnic episode compared to baseline values, i.e. pLTD developed (P = 0.023). In the 8- OH-DPAT group pPNA significantly decreased at T15, T30 and T60 compared to baseline, i.e. pLTD developed (P = 0.01). In the methysergide-treated group, acute intermittent hypercapnia did not evoke significant changes in pPNA at T15, T30, and T60 compared to baseline values. In the yohimbine group acute intermittent hypercapnia did not evoke significant changes of the peak phrenic nerve activity at T15, T30, and T60 compared to baseline values after the end of the last hypercapnic episode. In conclusion, activation of 5-HT1A receptors accentuated induction of pLTD, whereas blockade of α2-adrenergic receptors prevented development of pLTD following acute intermittent hypercapnia in anesthetized rats. These results suggest that chemical modulation of 5-HT and α2- adrenergic receptors in raphe nuclei affects hypercapnia induced pLTD, offering the important insights in understanding the mechanisms involved in development of respiratory plasticity.

central nervous system, respiratory plasticity, phrenic nerve, rats

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