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Am J Physiol Lung Cell Mol Physiol 274: L258-L263, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 2, L258-L263, February 1998

Inhibition of airway liquid secretion and its effect on the physical properties of airway mucus

Laura Trout1, Malcolm King2, Wei Feng2, Sarah K. Inglis1, and Stephen T. Ballard1

1 Department of Physiology, College of Medicine, University of South Alabama, Mobile, Alabama 36688; and 2 Mucobiology Research Unit, Heritage Medical Research Center, University of Alberta, Edmonton, Alberta, Canada T6G 2S2

The combination of both Cl- and HCO<SUP>−</SUP><SUB>3</SUB> secretion inhibitors causes an accumulation of mucins within the submucosal gland ducts of acetylcholine (ACh)-treated bronchi [S. K. Inglis, M. R. Corboz, A. E. Taylor, and S. T. Ballard. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L372-L377, 1997], suggesting indirectly that these agents block airway gland liquid secretion. The present study tested the hypotheses that ACh-stimulated liquid secretion is driven by Cl- and HCO<SUP>−</SUP><SUB>3</SUB> secretion and that inhibition of this process leads to secretion of a dehydrated mucus with altered rheological properties. Excised distal bronchi from pigs were pretreated with either a combination of Cl- and HCO<SUP>−</SUP><SUB>3</SUB> secretion inhibitors (bumetanide, acetazolamide, dimethylamiloride, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) or the dimethyl sulfoxide vehicle and were then treated with ACh to induce secretion. The rate of mucus liquid secretion was substantially reduced when the airways were pretreated with the anion secretion inhibitors. Mucus liquid from inhibitor-pretreated airways contained almost threefold more nonvolatile solids than the control liquid. Rheological analysis revealed that mucus liquid from inhibitor-pretreated airways expressed a significantly greater log G* (rigidity factor), whereas tangent delta  (recoil factor) was significantly reduced. These results suggest that 1) ACh-induced liquid secretion in bronchi is driven by both Cl- and HCO<SUP>−</SUP><SUB>3</SUB> secretion and 2) inhibition of ACh-induced liquid secretion results in the secretion of mucus with a reduced water content and altered rheological properties.

cystic fibrosis; bicarbonate secretion; chloride secretion; mucus rheology; distal bronchi


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