Bradykinin–evoked sensitization of airway sensory nerves: a mechanism for ace–inhibitor cough

ABSTRACT Cough accompanied by an increased sensitivity of the cough reflex is the most common symptom of inflammatory airway disease1,5. This symptom is also frequently reported in patients

receiving angiotensin–converting enzyme (ACE) inhibitors as therapy for heart failure or hypertension2–4, although the underlying mechanism is unknown. We have investigated the possibility

that the inflammatory peptide bradykinin, normally degraded by ACE, causes sensitization of airway sensory nerves and an enhancement of the cough reflex in conscious guinea pigs. Treatment

of guinea pigs for two weeks with captopril led to an increased cough response to inhaled citric acid, which was prevented by concomitant treatment with the bradykinin receptor antagonist

icatibant. A similar icatibant–sensitive enhancement of citric acid–evoked cough was seen in untreated animals after prior inhalation of bradykinin, although cough evoked by hypertonic

saline was unaffected. In electrophysiological studies performed _in vitro_, responses of single vagal C fibers to capsaicin, applied to receptive fields of single–fiber units in the

trachea, were also markedly increased after perfusion with bradykinin, whereas Aδ fiber responses to hypertonic saline were unaffected. These results indicate that bradykinin–evoked

sensitization of airway sensory nerves may underlie the pathogenesis of ACE–inhibitor cough. Bradykinin receptor antagonists may be of benefit in treating chronic cough seen with this and

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our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS LIPOPOLYSACCHARIDES INDUCE A RAGE-MEDIATED SENSITIZATION OF SENSORY NEURONS AND FLUID HYPERSECRETION IN THE UPPER

AIRWAYS Article Open access 16 April 2021 COUGH HYPERSENSITIVITY AND CHRONIC COUGH Article 30 June 2022 INHIBITORY MECHANISMS OF DOCOSAHEXAENOIC ACID ON CARBACHOL-, ANGIOTENSIN II-, AND

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Author notes * Alyson J. Fox and Umesh G. Lalloo: A.J.F. and U.G.L. contributed equally to this work. AUTHORS AND AFFILIATIONS * Department of Thoracic Medicine, National Heart &Lung

Institute, Dovehouse Street, London, SW3 6LY, UK Alyson J. Fox, Umesh G. Lalloo, Maria G. Belvisi, Micaela Bernareggi & Peter J. Barnes Authors * Alyson J. Fox View author publications

You can also search for this author inPubMed Google Scholar * Umesh G. Lalloo View author publications You can also search for this author inPubMed Google Scholar * Maria G. Belvisi View

author publications You can also search for this author inPubMed Google Scholar * Micaela Bernareggi View author publications You can also search for this author inPubMed Google Scholar * K.

Fan Chung View author publications You can also search for this author inPubMed Google Scholar * Peter J. Barnes View author publications You can also search for this author inPubMed Google

Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Fox, A., Lalloo, U., Belvisi, M. _et al._ Bradykinin–evoked sensitization of airway sensory

nerves: A mechanism for ACE–inhibitor cough. _Nat Med_ 2, 814–817 (1996). https://doi.org/10.1038/nm0796-814 Download citation * Received: 18 January 1995 * Accepted: 29 May 1996 *

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