Interaction between ion transporters and the mucociliary transport system in dog and baboon

Winters, Scot L., and Donovan B. Yeates. Interactionbetween ion transporters and the mucociliary transport system in dogand baboon. J. Appl. Physiol. 83(4):1348-1359, 1997.To gain insight into the role of epithelial ionchannels, pumps, and cotransporters in regulating airway water andmucociliary transport, we administered inhibitors of theNa⁺ channel (amiloride),3Na-2K-adenosinetriphosphatase (acetylstrophanthidin), and Na-K-2Clcotransporter (furosemide) to anesthetized dogs and/or baboons.Tracheal ciliary beat frequency was measured by using heterodyne laserlight scattering. Tracheal mucus velocity (TMV) and bronchialmucociliary clearance (BMC) or lung mucociliary clearance were measuredby using radioaerosols and nuclear imaging. Respiratory tract fluidoutput was collected by using a secretion-collecting endotracheal tube.In six dogs, amiloride aerosol [lung deposition, 96 ± 11 µg(means ± SE)] had minimal effect, whereasacetylstrophanthidin aerosol (lung deposition, 71 ± 9 µg)increased BMC, and furosemide (40 mg iv) markedly increased TMV. Infive 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. Indogs, respiratory tract fluid output increased after intravenousfurosemide from 2.2 ± 0.5 to 6.8 ± 1.7 mg/min. When combinedwith dry-air inhalation, furosemide failed to stimulate TMV andreversed the inhibition of BMC by dry air. Thus pharmacological manipulation of the Na-K-2Cl cotransporter and the3Na-2K-adenosinetriphosphatase pump may provide increases of clinicalrelevance in airway hydration and mucociliary transport.