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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that bradykinin may play a role in stimulating cough in at least one pathological condition in humans. We have employed an animal model to investigate the possible role of this peptide in irritant-induced cough. The kinin antagonist Hoe 140 and codeine both produced dose-related inhibition of cough responses to inhalation of citric acid or bradykinin aerosols by conscious guinea pigs. The selective tissue kallikrein inhibitor CH694 inhibited cough caused by citric acid but not by bradykinin. Indomethacin pretreatment attenuated the responses to both stimuli as did phosphoramidon. It is concluded that cough produced by citric acid inhalation may be mediated, at least in part, by generation of kinins; secondary to this, a release of prostanoids also appears to participate in the response.
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PMID:Mechanism of irritant-induced cough: studies with a kinin antagonist and a kallikrein inhibitor. 879 Dec 63

One adverse effect of the angiotensin-converting enzyme (ACE) inhibitors used for treatment of hypertension and congestive heart failure is the production of dry coughs. Imidapril is a new type of ACE inhibitor with a very low incidence of coughs. The magnitude and the mechanism of cough potentiation of imidapril and other ACE inhibitors has been studied in guinea-pigs. In normal guinea-pigs single and repeated dosing of imidapril at 0.1 to 100 mg kg-1 had no effect on capasaicin- or citric acid-induced coughs. Single and repeated dosing of enalapril and captopril at 10 to 30 mg kg-1, respectively, significantly increased the number of capsaicin-induced coughs. Repeated dosing of 1 mg kg-1 enalapril also significantly augmented the capsaicin cough. In bronchitic guinea-pigs imidapril also had no effect on the coughs induced by the two stimulants. Enalapril and captopril significantly increased the number of coughs induced not only by capsaicin but also by citric acid. Lower doses of enalapril were enough to augment the capsaicin-induced coughs, whereas medium to large doses failed to augment the cough irrespective of the protocol of administration. Bradykinin-induced discharges of the vegal afferents from the lower airway were significantly increased by enalaprilat but not by imidaprilat. Capsaicin-induced discharges of the afferents were, on the other hand, significantly depressed by enalaprilat, but not by imidaprilat. Interestingly, enalaprilat depression of the discharges was significantly reversed by Hoe-140, a bradykinin B2 receptor blocker. In guinea-pigs pretreated with a low dose of enalapril, arterial infusion of bradykinin significantly potentiated the coughs induced by capsaicin. The results indicated that imidapril was less potent than enalapril and captopril in potentiating cough responses induced by capsaicin and citric acid in guinea-pigs, and further suggest that bradykinin might be a key substance in the mechanism of the potentiation of coughs associated with ACE inhibitors.
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PMID:Studies on the magnitude and the mechanism of cough potentiation by angiotensin-converting enzyme inhibitors in guinea-pigs: involvement of bradykinin in the potentiation. 895 4

The use of angiotensin-converting enzyme (ACE) has been associated with the occurrence of adverse effects, including cough and angioneurotic edema. Accumulation of kinins has been suggested to play a major role in these adverse effects of ACE inhibitor, although conclusive evidence for such a role is lacking. We investigated whether ACE inhibition increases plasma extravasation in mice (Swiss, C57Bl/6J, and J129Sv/Ev strains) via inhibition of bradykinin metabolism and stimulation of neurogenic inflammatory mechanisms. Intravenous captopril and enalapril increased the extravasation of Evans blue dye in all tissues examined (trachea, stomach, duodenum, and pancreas). This effect was evident 15 minutes after drug administration. The particulate dye Monastral blue identified the sites of captopril-induced leakage in the microvasculature. Pretreatment with the bradykinin B2 receptor antagonist Hoe 140 or with the tachykinin NK1 receptor antagonist SR 140333 inhibited captopril-evoked increase in plasma extravasation. In mice in which the gene encoding the bradykinin B2 receptor was disrupted by gene targeting, neither bradykinin nor captopril increased plasma extravasation. Pretreatment with Hoe 140 did not reduce the hypotensive response induced by captopril. The present findings suggest that ACE inhibition increases kinin levels in tissues and/or plasma. These increased kinin levels increase microvascular leakage in mouse airways and digestive tract via the release of tachykinins from terminals of primary sensory neurons. Exaggerated kinin production and the subsequent stimulation of peptide release from sensory nerves may be involved in adverse effects of ACE inhibitors.
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PMID:Acute ACE inhibition causes plasma extravasation in mice that is mediated by bradykinin and substance P. 962 45