Fuller D D, Zabka A G, Baker T L, Mitchell G S
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706, USA.
J Appl Physiol (1985). 2001 May;90(5):2001-6; discussion 2000. doi: 10.1152/jappl.2001.90.5.2001.
Episodic hypoxia evokes a sustained augmentation of respiratory motor output known as long-term facilitation (LTF). Phrenic LTF is prevented by pretreatment with the 5-hydroxytryptamine (5-HT) receptor antagonist ketanserin. We tested the hypothesis that 5-HT receptor activation is necessary for the induction but not maintenance of phrenic LTF. Peak integrated phrenic nerve activity (integralPhr) was monitored for 1 h after three 5-min episodes of isocapnic hypoxia (arterial PO(2) = 40 +/- 2 Torr; 5-min hyperoxic intervals) in four groups of anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats [1) control (n = 11), 2) ketanserin pretreatment (2 mg/kg iv; n = 7), and ketanserin treatment 0 and 45 min after episodic hypoxia (n = 7 each)]. Ketanserin transiently decreased integralPhr, but it returned to baseline levels within 10 min. One hour after episodic hypoxia, integralPhr was significantly elevated from baseline in control and in the 0- and 45-min posthypoxia ketanserin groups. Conversely, ketanserin pretreatment abolished phrenic LTF. We conclude that 5-HT receptor activation is necessary to initiate (during hypoxia) but not maintain (following hypoxia) phrenic LTF.
间歇性低氧会引发呼吸运动输出的持续增强，即长期易化（LTF）。膈神经LTF可通过用5-羟色胺（5-HT）受体拮抗剂酮色林预处理来预防。我们检验了这样一个假说，即5-HT受体激活对于膈神经LTF的诱导是必要的，但对于其维持并非必要。在四组麻醉、迷走神经切断、麻痹并通气的Sprague-Dawley大鼠中，在经历三次5分钟的等碳酸低氧发作（动脉血氧分压 = 40 ± 2 Torr；5分钟高氧间隔）后，监测膈神经活动峰值积分（integralPhr）1小时[1）对照组（n = 11），2）酮色林预处理组（静脉注射2 mg/kg；n = 7），以及在间歇性低氧后0分钟和45分钟给予酮色林治疗组（每组n = 7）]。酮色林使integralPhr短暂降低，但在10分钟内恢复到基线水平。间歇性低氧1小时后，对照组以及低氧后0分钟和45分钟给予酮色林组的integralPhr较基线显著升高。相反，酮色林预处理消除了膈神经LTF。我们得出结论，5-HT受体激活对于启动（低氧期间）而非维持（低氧后）膈神经LTF是必要的。
