Parvez Omar, Voss Anne-Marie, de Kok Mascha, Roth-Kleiner Matthias, Belik Jaques
Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada, M5G IX8.
Pediatr Res. 2006 Jun;59(6):756-61. doi: 10.1203/01.pdr.0000219121.15634.d1. Epub 2006 Apr 26.
Aside for the potential for tonic contraction, the airway smooth muscle exhibits intermittent phasic rhythmic activity that may contribute to lung growth during fetal life. Therefore, we examined 4th generation rat 18-22 d gestation fetal, 4-6 d of age newborn and adult bronchial ring from Sprague Dawley rats to compare differences in smooth muscle function. We hypothesized that phasic contractions were greatest before birth. Bronchial muscle spontaneous rhythmic contractions were greatest in the fetus and absent in the adult. In response to KCl stimulation, the fetal bronchial smooth muscle only developed tonic force that was 3.5 +/- 0.6 and lower than measured in the newborn 9.0 +/- 0.3 and adult 13.7 +/- 1.4 mN/mm2. The thromboxane A2 analogue U46619 induced tonic and phasic muscle contractions and the amplitude and frequency of the phasic contractions were greater in the fetus as compared with the adult and increased with gestational age. The U46619-induced rhythmic contractions were abrogated by ryanodine, thapsigargin and reduction of extracellular Na+, suggesting intracellular Ca2+ dependence and involvement of the Na+/Ca2+ exchanger. The inward rectifier K+ blocker BaCl2 induced phasic contractions in unstimulated fetal, but not adult bronchial muscle of the same amplitude and frequency as for the spontaneous and U46619-induced ones. We conclude that the airway smooth muscle phasic activity is greatest in the fetus and tends to disappear post-natally with age suggesting an in utero role during lung development.
除了存在强直性收缩的可能性外,气道平滑肌还表现出间歇性的节律性活动,这可能有助于胎儿期肺的生长。因此,我们研究了来自Sprague Dawley大鼠的妊娠18 - 22天的第4代胎鼠、4 - 6日龄的新生鼠和成鼠的支气管环,以比较平滑肌功能的差异。我们假设节律性收缩在出生前最为强烈。支气管肌肉的自发节律性收缩在胎儿中最强,在成鼠中则不存在。在氯化钾刺激下,胎儿支气管平滑肌仅产生强直性张力,为3.5±0.6,低于新生鼠的9.0±0.3和成年鼠的13.7±1.4 mN/mm2。血栓素A2类似物U46619可诱导强直性和节律性肌肉收缩,与成年鼠相比,胎儿期节律性收缩的幅度和频率更大,且随胎龄增加。U46619诱导的节律性收缩可被ryanodine、毒胡萝卜素和细胞外钠离子减少所消除,提示其依赖细胞内钙离子且涉及钠/钙交换器。内向整流钾通道阻滞剂氯化钡可在未受刺激的胎儿支气管肌肉中诱导出与自发和U46619诱导的收缩幅度和频率相同的节律性收缩,但在成年支气管肌肉中则不会。我们得出结论,气道平滑肌的节律性活动在胎儿期最强,出生后随年龄增长往往会消失,这表明其在子宫内对肺发育具有一定作用。