Effect of neutral endopeptidase inhibitor on bradykinin-induced bronchoconstriction
| Autor: | Izumi Hayashi, Kazui Soma, Takashi Ohwada, Yoshito Kamijo, Masataka Majima |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Indoles Bronchoconstriction Neurokinin A Guinea Pigs Bradykinin Substance P General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Piperidines Internal medicine medicine Animals Drug Interactions General Pharmacology Toxicology and Pharmaceutics Lung Neprilysin Dose-Response Relationship Drug Phosphoramidon Glycopeptides Antagonist Metalloendopeptidases Dipeptides General Medicine respiratory system Endocrinology chemistry Benzamides NK1 receptor antagonist Capsaicin medicine.symptom Bronchoalveolar Lavage Fluid Drug Antagonism |
| Zdroj: | Life Sciences. 70:1-15 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/s0024-3205(01)01361-3 |
| Popis: | To evaluate whether neutral endopeptidase (NEP) inhibitors have adverse respiratory effects, the influence of a NEP inhibitor on bradykinin (BK)-induced bronchoconstriction was investigated. In anesthetized and artificially ventilated guinea pigs, changes in airway opening pressure (Pao) were measured as an index of bronchoconstriction. An infusion of phosphoramidon (3 mg kg −1 h −1 ), a NEP inhibitor, significantly enhanced the bronchoconstriction induced by high-dose BK (30 nmol kg −1 , i.v.). Capsaicin (0.1 mg kg −1 , i.v.) and SR48968 (0.3 mg kg −1 , i.v.), an NK2 receptor antagonist, significantly inhibited the phosphoramidon-induced enhancement of BK-induced bronchoconstriction, although FK888 (3 mg kg −1 , i.v.), an NK1 receptor antagonist, did not. Both neurokinin A (NKA) (0.1–3 nmol kg −1 , i.v.) and substance P (SP) (0.1–3 nmol kg −1 , i.v.) induced dose-dependent bronchoconstriction which was enhanced by phosphoramidon infusion, although these enhancements were more prominent in the NKA series. Phosphoramidon partially inhibited BK degradation in lung homogenate, and both NKA and SP degradation in the lung homogenate were significantly suppressed by phosphoramidon. In bronchoalveolar lavage fluid (BALF), levels of NKA and SP were significantly elevated after a bolus of BK with a phosphoramidon infusion. These results suggest that NEP inhibitors may have adverse respiratory effects resulting from inhibition of the degradation of neurokinins, but mainly of NKA, when a large amount of BK is generated. |
| Databáze: | OpenAIRE |
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