Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
Exp Neurol. 2020 Nov;333:113429. doi: 10.1016/j.expneurol.2020.113429. Epub 2020 Jul 29.
Moderate acute intermittent hypoxia (AIH) elicits a persistent, serotonin-dependent increase in phrenic amplitude, known as phrenic long-term facilitation (pLTF). Although pLTF was originally demonstrated by carotid sinus nerve stimulation, AIH still elicits residual pLTF in carotid denervated (CBX) rats via a distinct, but unknown mechanism. We hypothesized that exaggerated hypoxia-induced hypotension after carotid denervation leads to greater spinal tissue hypoxia and extracellular adenosine accumulation, thereby triggering adenosine 2A receptor (A)-dependent pLTF. Phrenic activity, arterial pressure and spinal tissue oxygen pressure were measured in anesthetized CBX rats. Exaggerated hypoxia-induced hypotension after CBX was prevented via intravenous phenylephrine; without the hypotension, spinal tissue hypoxia during AIH was normalized, and residual pLTF was no longer observed. Spinal A (MSX-3), but not serotonin 2 receptor (5-HT) inhibition (ketanserin), abolished residual pLTF in CBX rats. Thus, pLTF regulation may be altered in conditions impairing sympathetic activity and arterial pressure regulation, such as spinal cord injury.
中度急性间歇性低氧（AIH）会引起膈神经幅度的持续、依赖于 5-羟色胺的增加，这种现象被称为膈神经长期易化（pLTF）。尽管 pLTF 最初是通过颈动脉窦神经刺激来证明的，但在颈动脉去神经（CBX）大鼠中，AIH 仍然通过一种不同但未知的机制引起残余的 pLTF。我们假设颈动脉去神经后过度的低氧诱导性低血压会导致脊髓组织缺氧和细胞外腺苷积累增加，从而触发腺苷 A2A 受体（A）依赖性 pLTF。在麻醉的 CBX 大鼠中测量膈神经活动、动脉压和脊髓组织氧压。通过静脉注射苯肾上腺素预防 CBX 后过度的低氧诱导性低血压；没有低血压，AIH 期间的脊髓组织缺氧正常化，不再观察到残余的 pLTF。脊髓 A（MSX-3），而不是 5-羟色胺 2 受体（5-HT）抑制（酮色林），消除了 CBX 大鼠中的残余 pLTF。因此，在损害交感神经活动和动脉血压调节的情况下，如脊髓损伤，pLTF 的调节可能会发生变化。
