Clonidine在臨床上是用來作為降高血壓的藥物之一，但是長期服用的患者往往會出現呼吸不順、睡眠呼吸終止的症狀，暗指可能與上呼吸道運暢通的問題有關。管制上呼吸道暢通的運動神經如舌下神經與喉返神經的活動，包含吸氣活動與吸氣前活動，而這兩種時期的放電活動能調控上呼吸道氣流的阻力，對於上呼吸道暢通扮演重要的角色。推測clonidine可能會抑制上呼吸道運動神經的吸氣活動與吸氣前活動，因此而影響上呼吸道的暢通。本論文的目的是探討clonidine對大鼠上呼吸道運動神經吸氣與吸氣前活性的影響，但是由於吸氣前活性高度的計算不易，因此本論文透過提高呼氣末正壓以及切斷兩側迷走神經的方式，促使吸氣前活性增強，以利實驗的觀察。結果顯示，clonidine對於舌下與喉返神經吸氣前活性的抑制作用呈現劑量反應，且clonidine的抑制作用會被a2-adrenergic receptor作用劑yohimbine所阻斷，且yohimbine的作用會促使舌下神經與喉返神經活動明顯提高，暗示clonidine可能是藉由2-adrenergic receptor來改變呼吸型態。此外，增加呼氣末正壓會產生抑制吸氣、促進吸氣前活動，於是發生分離反應，這種分離反應也在給予clonidine之後消失。切斷兩側迷走神經後，吸氣前活動更為提前、且活動更高，這種反應也會被clonidine所阻斷。綜合這些結果，顯示了幾個結論：(1) clonidine造成呼吸困難等副作用可能是由於抑制了上呼吸道運動神經吸氣前活動所導致。(2) 2-adrenergic receptor在正常情況下對於上呼吸道運動神經的吸氣前活性就會有持續性的抑制作用，此外，clonidine可能是藉由興奮2-adrenergic receptor來抑制上呼吸道運動神經的吸氣前活性。(3) clonidine不但會抑制了由呼氣末正壓所興奮的吸氣前活動，同時也將殘存的吸氣活性給完全抑制，這暗示著clonidine可能會促進呼氣末正壓對於吸氣活動的抑制作用。(4) clonidine對上呼吸道吸氣前活性的抑制作用可能不是藉由迷走神經的影響，同時，也進一步的推測，2-adrenergic receptor可能也參與了迷走傳入神經對舌下吸氣前活性的調控作用。

Clonidine is one of the clinical drugs used for the treatment of hypertension. However, it has been demonstrated that the patients who took this drug chronically would develop some symptoms such as respiratory disorder and sleep apnea syndrome. These symptoms have been considered as to be relative to the disturbance of the upper airway (UAW) patency which is regulated by the UAW motor nerve activities. Onset of the UAW motor output activities precede the prenic burst commencement, termed pre-inspiratory (pre-I) activity, and thus the UAW motor output exhibit inspiratory (I) and pre-I activity. These I and pre-I activities may play an important role in maintaining a patent UAW. We hypothesize that clonidine might have produced an inhibitory effect on both the I and pre-I activities. Purpose of present study was to investigate the influences of clonidine administration on UAW motor output in the rat. We simultaneously recorded activities of the phrenic, hypoglossal and recurrent laryngeal nerves in anesthetized rats. To produce a more clear pre-I activity, we enhanced the pre-I activity, both increase in ampltitude and more advancement in onset, by changing positive end-expired pressure (PEEP) and cutting the vagi bilaterally. The results showed that administration of clonidine produced a dose-dependent inhibition of pre-I activity. This inhibition was blocked by yohimbine, an a2-adrenergic antagonist. PEEP at 9 cmH2O produced an increase in pre-I activity reflecting a higher amplitude and a more advancement of onset time and induced also uncoupled activity. This increase in pre-I activity was inhibited by administration of clonidine and thus a decrease of percentage of the uncoupled activity was obtained. Bilateral vagotomy also produced an excitation to the pre-I activity which was inhibited by clonidine administration. In conclusion, the present results suggest that (1) clonidine administration may produce inhibition on the pre-I activity of UAW motor output; (2) a2-adrenergic receptor may mediate this inhibition of clonidine impinging on the pre-I and may have a tonic inhibition on the pre-I activity of UAW motor nerve; (3) administration of clonidine not only inhibited the uncoupled activity induced by PEEP but also blocked the I activity; and (4) the inhibition of clonidine on the pre-I activity was remained after bilateral vagotomy. These results strongly suggest that a2-adrenergic receptor may participate in the modulation of the pre-I activity of the UAW motor outputs.

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