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HOCl causes airway substance P hyperresponsiveness and neutral endopeptidase hypoactivity.
Murlas CG; Murphy TP; Lang Z
Am J Physiol, Lung Cell Mol Physiol 1990 Jun; 258(6):L361-L368
Guinea-pig tracheal tissue was exposed to hypochlorous-acid (7790923) (HOCl) or hydrogen-peroxide (7722841) (H2O2) in an effort to determine whether there would be any effect on the responsiveness of airway muscle to acetylcholine (ACh), potassium-chloride (KCl), or substrate-P in the presence or absence of phosphoramidon. Tracheas were isolated from male Hartley-guinea-pigs, and used for airway contraction studies. Tissues were exposed to HOCl or H2O2 by perfusion through the airway lumen. A hyperresponsiveness to substance-P was noted in smooth muscle of mucosa intact guinea-pig airways which had been perfused with HOCl but not H2O2. No hyperreactivity was noted in response to ACh or KCl. Phosphoramidon pretreated, HOCl perfused rings behaved the same as Krebs solution exposed controls. An association between hyperresponsiveness and decreased neutral endopeptidase (NEP) activity was noted. In studying the catabolism of substance-P, it was noted that HOCl or phosphoramidon exposure decreased substance-P disappearance from the perfusates. The authors suggest that smooth muscle hyperresponsiveness to substance-P caused by the perfusion of airways with HOCl occurs through HOCl inactivation of mucosal NEP.
NIOSH Publication; NIOSH Grant; Pulmonary system disorders; Enzyme activity; Laboratory animals; Respiratory irritants; Oxidizers; Lung irritants; Mucous membranes; Author Keywords: airway hyperreactivity; asthma; bronchoconstriction; bronchial reactivity; enkephalinase; guinea pig; hypohalous acids; metalloendopeptidase; muscarinic receptors; oxidant injury; tachykinins; trachealis muscle
Christopher G. Murlas, Internal Medicine Univ of Tennessee, Memphis 956 Court Avenue Memphis, TN 38163
Issue of Publication
American Journal of Physiology: Lung Cellular and Molecular Physiology
University of Cincinnati, Cincinnati, Ohio
Page last reviewed: June 15, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division