| Enhanced airway responses to substance P after repeated challenge in guinea pigs. | |
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MedLine Citation:
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PMID: 2468638 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We performed three consecutive dose-response curves to rapid intravenous infusions of substance P (SP) in anesthetized, mechanically ventilated guinea pigs. The dose of SP required to decrease pulmonary conductance to 50% of its base-line value (ED50GL) decreased 2.8-fold (P less than 0.002) and 3.3-fold (P less than 0.001) on the second and third dose-response curves, respectively, compared with the first. SP did not alter airway responses to intravenous histamine but did cause a significant (3.7-fold) decrease in ED50GL for dose-response curves to intravenous capsaicin, an agent that causes bronchoconstriction by release of endogenous tachykinins. The neutral metalloendopeptidase inhibitor thiorphan (0.5 mg) and the angiotensin-converting enzyme inhibitor captopril (1.7 mg) both caused a marked enhancement of airway responses to SP observed on the first dose-response curve but did not alter the enhancement of SP-induced airway responses produced by repeated SP challenge. The anticholinergic atropine (5 mg/kg iv), the antihistamine mepyramine (8 mg/kg iv), and the cyclooxygenase inhibitor indomethacin (30 mg/kg ip) had no effect on the first SP dose-response curve. Atropine and mepyramine did not prevent the enhancement of SP responses observed with repeated challenge, but after pretreatment with either indomethacin or acetylsalicylic acid, dose-response curves to SP were reproducible. Our results indicate that airway responses to intravenous SP are enhanced with repeated SP challenge and suggest that cyclooxygenase products of arachidonic acid metabolism are involved in the mediation of this phenomenon. |
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Authors:
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S A Shore; J M Drazen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of applied physiology (Bethesda, Md. : 1985) Volume: 66 ISSN: 8750-7587 ISO Abbreviation: J. Appl. Physiol. Publication Date: 1989 Feb |
Date Detail:
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Created Date: 1989-06-02 Completed Date: 1989-06-02 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8502536 Medline TA: J Appl Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 955-61 Citation Subset: IM |
Affiliation:
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Department of Medicine, Beth Israel Hospital, Boston, Massachusetts. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atropine / pharmacology Capsaicin / pharmacology Dose-Response Relationship, Drug Guinea Pigs Histamine / pharmacology Indomethacin / pharmacology Lung Compliance / drug effects Male Muscle Contraction / drug effects Pyrilamine / pharmacology Respiratory Physiological Phenomena Respiratory System / drug effects* Substance P / administration & dosage, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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HL-39827/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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33507-63-0/Substance P; 404-86-4/Capsaicin; 51-45-6/Histamine; 51-55-8/Atropine; 53-86-1/Indomethacin; 91-84-9/Pyrilamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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