Winters, Scot L., and Donovan B. Yeates. Interaction between ion transporters and the mucociliary transport system in dog and baboon. J. Appl. Physiol. 83(4): 1348–1359, 1997.—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 μg (means ± SE)] had minimal effect, whereas acetylstrophanthidin aerosol (lung deposition, 71 ± 9 μg) 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 μm/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.
Construction of a Suite of Computable Biological Network Models Focused on Mucociliary Clearance in the Respiratory Tract
