Effect of chronic hypoxia on calcium signalling in airway smooth muscle cells

Chronic hypoxia (CH) alters smooth muscle contractility. CII generally produces a sustained attenuation of vasoreactivity. In airways, this effect of CH is poorly understood although CH is frequently observed in patients with pulmonary diseases. This study was designed to examine the effect of CH on both the isometric contraction of isolated rings and the cytosolic calcium concentration ([Ca2+])i using micro-spectrofluorimetry in freshly isolated cells from rat tracheal smooth muscle. Tissues were obtained from both chronically hypoxic rats maintained in a hypobaric chamber (50.5 kPa) for 15 days and normoxic animals. CH increased the sensitivity of airway smooth muscle to cholinergic agonists. This increase observed in the mechanical activity (concentration of carbachol producing 50% of the maximal force (EC50) in tissues from normoxic and hypoxic animals: 0.80 mu M (0.39-1.21 mu M) and 0.34 mu M (0.08-0.59 mu M), respectively, p<0.05) was related to an increase in the sensitivity of cholinergic-mediated Ca2+ release (acetylcholine EC50 in cells from normoxic and hypoxic animals: 0.14 mu M (0.11-0.17 mu M) and 0.04 mu M (0.026-0.054 mu M), respectively, p<0.05). It was concluded that chronic hypoxia alters calcium signalling in airway smooth muscle cells, which was associated with an increase in airway responsiveness in vitro. Whether a similar phenomenon contributes to bronchial hyperresponsiveness in chronically hypoxaemic patients remains to be established.