引用

急性间歇性缺氧(AIH)通过一种需要脊髓血清素(5-HT)受体激活和NADPH氧化酶(NOX)活性的机制诱导膈肌长期易化(pLTF)。在这里，我们研究了:(1)脊髓一氧化氮合酶(NOS)活性对aih诱导的pLTF是否必要;(2)间发性外源性一氧化氮(NO)足以引起膈肌运动促进(pMF)而不引起AIH(即药理学上);no诱导的pMF需要脊髓5-HT2B受体和NOX激活。在麻醉、机械通气的成年雄性大鼠，AIH(3次5分钟;O2 10%;5 min)引起综合膈神经爆发(即pLTF)振幅进行性增加，持续时间为aih后60 min(45.1% 8.6%基线)。在膈肌运动核附近鞘内注射神经元NOS抑制剂(nNOS-inhibitor-1)的预处理使pLTF减弱(14.7 2.5%)，而诱导性NOS (iNOS)抑制剂(1400 W)没有效果(56.3% 8.0%)。间断静脉注射(3 5l容积;5分钟)的NO供体(硝普钠; SNP) elicited pMF similar in time-course and magnitude (40.4 6.0%, 60 min post-injection) to AIH-induced pLTF. SNP-induced pMF was blocked by a 5-HT2B receptor antagonist (SB206553), a superoxide dismutase mimetic (MnTMPyP), and two NOX inhibitors (apocynin and DPI). Neither pLTF nor pMF was affected by pre-treatment with a protein kinase G (PKG) inhibitor (KT-5823). Thus, spinal nNOS activity is necessary for AIH-induced pLTF, and episodic spinal NO is sufficient to elicit pMF by a mechanism that requires 5-HT2B receptor activation and NOX-derived ROS formation, which indicates AIH (and NO) elicits spinal respiratory plasticity by a nitrergic-serotonergic mechanism.