engleski

Contribution of noradrenergic inputs to hypoglossal motoneuron (IHMN) activity in decerebrate dogs

Introduction: Inspiratory hypoglossal motoneurons(IHMNs) contribute to upper airway patency during sleep and anesthesia.Noradrenergic excitatory input contributes to phasic and tonic genioglossus activity in wakefulness and non-REM sleep in freely behaving rats.We hypothesized that noradrenergic inputs to IHMNs also contribute to their activity in decerebrate dogs.We studied the effect of the adrenergic α-1 receptor agonist Phenylephrine (Phe), the α-2 agonist Medetomidine (Med), the α-1 antagonist Prazosin (Pra) and the α-2 antagonist Yohimbine (Yoh) on the discharge patterns of single IHMN. Methods: Dogs were vagotomized and decerebrate under isoflurane anesthesia and studied during isohypercapnic hyperoxia in the absence of anesthesia, while being mechanically ventilated.IHMNs were located in the brainstem via stereotaxic coordinates, response to picoejection of 5HT and by discharge pattern.Multibarrel micropipettes were used to record extracellular activity and picoeject agonists (Phe:100µM, Med:10µM) or antagonists (Pra:50µM, Yoh:100µM) on single IHMNs in vivo.Drug-induced changes in discharge frequency (Fn) patterns were analyzed using cycle-triggered histograms.Statistical analysis was performed comparing control Fn to Fn during drug application.Plots of Fn patterns during drug application vs. control conditions were analyzed by linear regression.Repeated measures ANOVA and post hoc procedures were used to test for significant differences (p< 0.05). Results: Four protocols were performed.In protocol 1 we picoejected α-1 and α-2 agonists.Phe increased the peak inspiratory discharge Fn to 148+-39% (p=0.001) of control and the average Fn to 145±36% (p=0.003), while Med did not have any effect:only α-1 receptors are present on IHMNs.In protocol 2 Phe increased the peak Fn to 151±31% (p< 0.012) and ave Fn to 148±27% (p=0.003).Pra did not produce any significant effect but completely reversed the Phe effects to control level.In protocol 3 both Med and Yoh did not produce significant changes.In protocol 4 Pra and Yoh also did not produce any significant changes:no endogenous activation. Conclusion: Picoejection of α-1 agonist Phe on single IHMNs produced significant increase in Fn confirming the presence of α-1 adrenergic receptors. However, neither α-1 nor α-2 antagonists produced any significant changes. This suggests that even though α-1 receptors are present on IHMNs, there is no significant endogenous noradrenergic excitatory drive contributing to IHMN activity

α-1 agonist ; IHMN ; dog ; upper airway patency

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