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

Chronic hypoxia (CH) alters smooth muscle contractility. CII generally prod uces 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 c ontraction of isolated rings and the cytosolic calcium concentration ([Ca2])i using micro-spectrofluorimetry in freshly isolated cells from rat trach eal smooth muscle. Tissues were obtained from both chronically hypoxic rats maintained in a hypobaric chamber (50.5 kPa) for 15 days and normoxic anim als. CH increased the sensitivity of airway smooth muscle to cholinergic agonist s. This increase observed in the mechanical activity (concentration of carb achol producing 50% of the maximal force (EC50) in tissues from normoxic an d 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 c holinergic-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 s mooth muscle cells, which was associated with an increase in airway respons iveness in vitro. Whether a similar phenomenon contributes to bronchial hyp erresponsiveness in chronically hypoxaemic patients remains to be establish ed.