Mechanosensitivity is hypothesized to participate in the regulation of ciliary beat frequency (CBF) in airway epithelia. To investigate this hypothesis, CBF in excised mouse trachea was monitored (microscopy image analysis) while varying mucosal shear (perfusate velocity and/or viscosity; planar flow). CBF increased within minutes of step increase to steady shear stress as small as 10(-3) Pa and decreased within minutes of shear reduction (

To gain insight into the homeostatic mechanisms regulating airway ion/water fluxes and mucociliary transport, the canine tracheobronchial airway fluid was perturbed by deposition of hypo- and hyperosmotic aerosols for >1 h. Tracheal ciliary beat frequency (CBF) was measured by using heterodyne laser light scattering. Tracheal mucus velocity (TMV) and bronchial mucociliary clearance (BMC) were measured by using radioaerosols and nuclear imaging. Respiratory tract fluid output (RTFO) was collected by using a secretion-collecting endotracheal tube. In six dogs, CBF increased during water deposition in the airways to 180 +/- 30 mg/min and RTFO increased from 2.2 +/- 0.5 to 18.3 +/- 1.6 mg/min, accounting for <10% of the fluid deposition. TMV and BMC were unchanged. CBF, TMV, and BMC were markedly increased by inhalation of aerosolized 3.4 M NaCl. Aerosolized 0.85 M NaCl, in contrast, decreased BMC. In this case, RTFO represented 24% of aerosol deposition. Aerosolized 0.85 M choline chloride and 0.85 M sodium gluconate enhanced BMC and TMV concurrent with a decrease in CBF. RTFO of sodium gluconate studies exceeded 50% of aerosol deposition. Thus the airways appear to have transepithelial compensatory mechanisms that reduce the impact of a moderate increases in NaCl and hydration load, but when these responses cannot adequately respond because of the delivery of impermeable ions or very high tonicity, removal of the challenges are affected by a stimulation of mucociliary transport.

To gain insight into the role of epithelial ion channels, pumps, and cotransporters in regulating airway water and mucociliary transport, we administered inhibitors of the Na+ channel (amiloride), 3Na-2K-adenosinetriphosphatase (acetylstrophanthidin), and Na-K-2Cl cotransporter (furosemide) to anesthetized dogs and/or baboons. Tracheal ciliary beat frequency was measured by using heterodyne laser light scattering. Tracheal mucus velocity (TMV) and bronchial mucociliary clearance (BMC) or lung mucociliary clearance were measured by using radioaerosols and nuclear imaging. Respiratory tract fluid output was collected by using a secretion-collecting endotracheal tube. In six dogs, amiloride aerosol -lung deposition, 96 +/- 11 microg (means +/- SE)- had minimal effect, whereas acetylstrophanthidin aerosol (lung deposition, 71 +/- 9 microg) increased BMC, and furosemide (40 mg iv) markedly increased TMV. In five baboons, TMV increased after iv furosemide administration (2 mg/kg) as well as by aerosol (lung deposition, 20 +/- 3 mg), coincident with increases in ciliary-mucus coupling from 11.5 +/- 0. 1 to 29.5 +/- 0.4 and 46.5 +/- 0.7 microm/beat, respectively. Furosemide also increased lung mucociliary clearance in baboons. In dogs, respiratory tract fluid output increased after intravenous furosemide from 2.2 +/- 0.5 to 6.8 +/- 1.7 mg/min. When combined with dry-air inhalation, furosemide failed to stimulate TMV and reversed the inhibition of BMC by dry air. Thus pharmacological manipulation of the Na-K-2Cl cotransporter and the 3Na-2K-adenosinetriphosphatase pump may provide increases of clinical relevance in airway hydration and mucociliary transport.