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Intratracheal administration of phosphodiesterase III inhibitor attenuates bronchoconstriction in cats: A preliminary report
Author(s) -
Hu Hong,
Takata Masao,
Kusakawa Isao,
Fujita Michio,
Miyasaka Katsuyuki
Publication year - 1995
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.1950190609
Subject(s) - bronchoconstriction , methacholine , medicine , tachyphylaxis , saline , inhalation , cats , pharmacology , respiratory system , anesthesia , asthma , lung , respiratory disease
The effects of intratracheal administration of MKS 492, selective phosphodiesterase (PDE) 111 inhibitor, were studied in five anesthetized bronchoconstricted cats. The animals were challenged by four repeated doses of intratracheal methacholine (67 μg/kg), and the degree of bronchoconstriction was assessed from increases in respiratory system resistance (Rrs). All animals demonstrated good bronchoconstrictive responses (i.e., 86–99% increases in Rrs) to methacholine without tachyphylaxis. On separate day, the cats received the same four doses of methacholine after being pretreated with either intratrachael saline or three different doses of MKS 492 (0.17, 1.7, and 17 μg/kg). The increases in Rrs with 1.7 μg/kg [;52.6 ± 8.4% (SE)] and 17 μg/kg of MKS 492 (44.4 ± 10.1%) were smaller than those with saline pretreatment (88.1 ± 16.8%) ( P < 0.05). There were no treatment‐associated changes in mean arterial pressure or heart rate during administration of MKS 492. We conclude that intratracheal MKS 492 effectively reduced methacholine‐induced bronchoconstriction in dose‐dependent fashion without substantial systemic effects. These preliminary results suggest that inhalation of isozyme‐selective PDE inhibitors may deserve consideration for clinical trials provided that more extensive preclinical investigations justify such trials. © 1995 Wiley‐Liss, Inc.