engleski

THE ROLE OF ALPHA-2 ADRENERGIC RECEPTORS IN CAUDAL RAPHE REGION ON PLTD IN RATS

Introduction: Previous studies showed that intermittent hypercapnia may evoke phrenic long-term depression (pLTD), which manifests as prolonged depression of phrenic nerve activity. Adrenergic receptors have been shown to modulate pLTD, but the precise site of action has not been revealed. The present study investigated the role of alpha-2 adrenergic receptors in caudal raphe region in pLTD. Our hypothesis was that microinjections of alpha-2 adrenergic antagonist yohimbine into the caudal raphe nucleus could attenuate phrenic LTD after exposure to acute intermittent hypercapnia (AIHc). Materials and methods: Adult, male, urethane- anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats were exposed to AIHc protocol. Experimental group of animals (n=9) received microinjection of yohimbine (1 mM, 20±5 nl) into the caudal raphe region, whereas control group (n=7) received microinjection of 0.9% saline (20±5 nl) into the same region. Peak phrenic nerve activity (pPNA) and burst frequency (f) were analyzed during five hypercapnic episodes (THc1-5) and at 15, 30, and 60 minutes after the end of the last hypercapnia. Results: In the control group, pPNA decreased by 43.3±14.3 % at 60 minutes after the end of the last hypercapnic episode compared to baseline values, i.e. pLTD developed (P=0.023). Microinjections of yohimbine into the caudal raphe region prior to hypercapnic stimulation attenuated pLTD at one hour post-hypercapnia (pPNA increased by 35.5±46.7%, P>0.05). Conclusions: Microinjection of alpha-2 adrenergic receptors antagonist yohimbine into the caudal raphe nuclei attenuated pLTD following acute intermittent hypercapnia, suggesting that alpha-2 adrenergic receptors in the caudal raphe region are important for induction of pLTD.

respiratory plasticity; phrenic nerve; raphe region; rat

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