Abstract
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 ± 1.4mN/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.
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References
Mitzner W 2004 Airway smooth muscle: the appendix of the lung. Am J Respir Crit Care Med 169: 787–790
Fujiwara T, Itoh T, Kuriyama H 1988 Regional differences in the mechanical properties of rabbit airway smooth muscle. Br J Pharmacol 94: 389–396
Ito Y, Suzuki H, Aizawa H, Hakoda H, Hirose T 1989 The spontaneous electrical and mechanical activity of human bronchial smooth muscle: its modulation by drugs. Br J Pharmacol 98: 1249–1260
Davis C, Kannan MS, Jones TR, Daniel EE 1982 Control of human airway smooth muscle: in vitro studies. J Appl Physiol 53: 1080–1087
Tagliente TM, Dalton BA, Be Harari RR 1992 Phasic responses to carbachol in isolated guinea pig trachea are augmented by cooling and inhibited by nifedipine. J Pharmacol Exp Ther 261: 755–763
Richards IS, Kulkarni A, Brooks SM 1991 Human fetal tracheal smooth muscle produces spontaneous electromechanical oscillations that are Ca2+ dependent and cholinergically potentiated. Dev Pharmacol Ther 16: 22–28
McCray PB Jr 1993 Spontaneous contractility of human fetal airway smooth muscle. Am J Respir Cell Mol Biol 8: 573–580
Schittny JC, Miserocchi G, Sparrow MP 2000 Spontaneous peristaltic airway contractions propel lung liquid through the bronchial tree of intact and fetal lung explants. Am J Respir Cell Mol Biol 23: 11–18
Jesudason EC, Smith NP, Connell MG, Spiller DG, White MR, Fernig DG, Losty PD 2005 Developing rat lung has a sided pacemaker region for morphogenesis-related airway peristalsis. Am J Respir Cell Mol Biol 32: 118–127
Nakamura KT, McCray PB Jr 2000 Fetal airway smooth-muscle contractility and lung development. A player in the band or just someone in the audience?. Am J Respir Cell Mol Biol 23: 3–6
Moffatt JD, Cocks TM 2004 Pharmacologically distinct intracellular calcium pools regulate tonic and oscillatory responses in porcine thoracic duct. J Cardiovasc Pharmacol 43: 83–92
Belik J, Jankov RP, Pan J, Tanswell AK 2003 Chronic O2 exposure enhances vascular and airway smooth muscle contraction in the newborn but not adult rat. J Appl Physiol 94: 2303–2312
Shaw L, O'Neill S, Jones CJ, Austin C, Taggart MJ 2004 Comparison of U46619-, endothelin-1- or phenylephrine-induced changes in cellular Ca2+ profiles and Ca2+ sensitisation of constriction of pressurised rat resistance arteries. Br J Pharmacol 141: 678–688
Belik J, Kerc E, Pato MD 2006 Rat pulmonary arterial smooth muscle myosin light chain kinase and phosphatase activities decrease with age. Am J Physiol Lung Cell Mol Physiol 290: L509–L516
Wei L, Roberts W, Wang L, Yamada M, Zhang S, Zhao Z, Rivkees SA, Schwartz RJ, Imanaka-Yoshida K 2001 Rho kinases play an obligatory role in vertebrate embryonic organogenesis. Development 128: 2953–2962
Snetkov VA, Ward JP 1999 Ion currents in smooth muscle cells from human small bronchioles: presence of an inward rectifier K+ current and three types of large conductance K+ channel. Exp Physiol 84: 835–846
Lewis M 1924 Spontaneous rhythmical contraction of the muscles of the bronchial tubes and air sacs of the chick embryo. Am J Physiol 68: 385–388
Chideckel EW, Frost JL, Mike P, Fedan JS 1987 The effect of ouabain on tension in isolated respiratory tract smooth muscle of humans and other species. Br J Pharmacol 92: 609–614
Sollmann T, Gilbert AJ 1937 Microscopic observations on bronchiolar reactions. J Pharmacol Exp Ther 61: 272–285
Sato T, Hirota K, Matsuki A, Zsigmond EK, Rabito SF 1998 Ketamine inhibits the tonic response to carbachol and histamine in the guinea pig trachea. Eur J Anaesthesiol 15: 486–492
Himpens B 1992 Modulation of the Ca(2+)-sensitivity in phasic and tonic smooth muscle. Verh K Acad Geneeskd Belg 54: 217–251
McHale NG, Thornbury KD, Hollywood MA 2000 5-HT inhibits spontaneous contractility of isolated sheep mesenteric lymphatics via activation of 5-HT(4) receptors. Microvasc Res 60: 261–268
Potjer RM, Constantinou CE 1989 Frequency of spontaneous contractions in longitudinal and transverse bladder strips. Am J Physiol 257: R781–R787
Stork AP, Cocks TM 1994 Pharmacological reactivity of human epicardial coronary arteries: phasic and tonic responses to vasoconstrictor agents differentiated by nifedipine. Br J Pharmacol 113: 1093–1098
Greenberg SS, Wang Y, Xie J, Smartz L, Rammazatto L, Curro FA 1991 The effect of thromboxane on contraction of canine mesenteric and lingual arteries. J Dent Res 70: 1278–1285
Roman J 1995 Effects of calcium channel blockade on mammalian lung branching morphogenesis. Exp Lung Res 21: 489–502
Featherstone NC, Jesudason EC, Connell MG, Fernig DG, Wray S, Losty PD, Burdyga TV 2005 Spontaneous propagating calcium waves underpin airway peristalsis in embryonic rat lung. Am J Respir Cell Mol Biol 33: 153–160
Ohata H, Kawanishi T, Hisamitsu T, Takahashi M, Momose K 1996 Functional coupling of the Na+/Ca2+ exchanger with Ca2+ release from intracellular stores in cultured smooth muscle cells of guinea pig ileum. Life Sci 58: 1179–1187
Janssen LJ 2002 Ionic mechanisms and Ca(2+) regulation in airway smooth muscle contraction: do the data contradict dogma?. Am J Physiol Lung Cell Mol Physiol 282: L1161–L1178
Snetkov VA, Pandya H, Hirst SJ, Ward JP 1998 Potassium channels in human fetal airway smooth muscle cells. Pediatr Res 43: 548–554
Snetkov VA, Hirst SJ, Ward JP 1996 Ion channels in freshly isolated and cultured human bronchial smooth muscle cells. Exp Physiol 81: 791–804
Somlyo AP, Somlyo AV 2004 Signal transduction through the RhoA/Rho-kinase pathway in smooth muscle. J Muscle Res Cell Motil 25: 613–615
Wareing M, O'Hara M, Seghier F, Baker PN, Taggart MJ 2005 The involvement of Rho-associated kinases in agonist-dependent contractions of human maternal and placental arteries at term gestation. Am J Obstet Gynecol 193: 815–824
Ding X, Murray PA 2005 Cellular mechanisms of thromboxane A2-mediated contraction in pulmonary veins. Am J Physiol Lung Cell Mol Physiol 289: L825–L833
Wilson DP, Susnjar M, Kiss E, Sutherland C, Walsh MP 2005 Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of Ca2+ entry and Ca2+ sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem J 389: 763–774
Harding R, Hooper SB 1996 Regulation of lung expansion and lung growth before birth. J Appl Physiol 81: 209–224
Wigglesworth JS 1981 Pulmonary hypoplasia with phrenic nerve agenesis. J Pediatr 98: 667–668
Wigglesworth JS, Desai R 1979 Effect on lung growth of cervical cord section in the rabbit fetus. Early Hum Dev 3: 51–65
Higuchi M, Hirano H, Gotoh K, Otomo K, Maki M 1991 Relationship between the duration of fetal breathing movements and gestational age and the development of the central nervous system at 25-32 weeks of gestation in normal pregnancy. Gynecol Obstet Invest 31: 136–140
Kobayashi K, Lemke RP, Greer JJ 2001 Ultrasound measurements of fetal breathing movements in the rat. J Appl Physiol 91: 316–320
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This work was supported by an operating grant from the Canadian Institutes for Health and Research
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Parvez, O., Voss, AM., de Kok, M. et al. Bronchial Muscle Peristaltic Activity in the Fetal Rat. Pediatr Res 59, 756–761 (2006). https://doi.org/10.1203/01.pdr.0000219121.15634.d1
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DOI: https://doi.org/10.1203/01.pdr.0000219121.15634.d1
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