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Attenuation of tachykinin‐induced airflow obstruction and microvascular leakage in immature airways
Author(s) -
Tokuyama Kenichi,
Yokoyama Tatsuya,
Morikawa Akihiro,
Mochizuki Hiroyuki,
Kuroume Takayoshi,
Barnes Peter J.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13434.x
Subject(s) - phosphoramidon , extravasation , evans blue , neurokinin a , substance p , airway resistance , potency , neprilysin , bronchoconstriction , medicine , thiorphan , lung , endocrinology , chemistry , anesthesia , airway , pathology , neuropeptide , in vitro , biochemistry , receptor , enzyme
1 To study the effect of maturation on substance P (SP)‐ and neurokinin A (NKA)‐induced airflow obstruction and airway microvascular leakage (MVL), we have measured changes in both lung resistance (R L ) and extravasation of Evans blue dye in anaesthetized immature (aged 14 ± 1 days) and adult guinea‐pigs (aged 80 ± 3 days). 2 R L and its recovery after hyperinflation at 5 min were measured for 6 min after i.v. SP (0.2, 1 and 30 nmol kg −1 ), NKA (1 and 10 nmol kg −1 ) or vehicle (0.9% NaCl). After measurement of R L , MVL in trachea, main bronchi and intrapulmonary airways was also examined. 3 The order of potency in inducing airflow obstruction did not change with age (NKA> SP) but immature animals required a larger dose of SP or NKA than adults to cause a significant increase in R L . 4 The order of potency in inducing airway microvascular leakage was sp> NKA in both immature and adult animals. The amount of extravasated dye after SP was significantly less in immature airways, especially in central airways. 5 Phosphoramidon (2.5 mg kg −1 ), a neutral endopeptidase (NEP) inhibitor, significantly increased R L after 0.2 nmol kg −1 SP only in adult airways. Phosphoramidon enhanced the dye extravasation after 0.2 nmol kg −1 SP in both immature and adult airways with a significantly greater amount of dye in adult animals, suggesting that mechanisms other than changes in NEP activity may be responsible for this age‐related difference. 6 R L after hyperinflation following SP was not correlated with the degree of extravasation of Evans blue dye in immature animals, whereas it was closely correlated in adult animals. 7 SP and NKA may be less potent in causing both bronchoconstriction and microvascular leakage in immature airways. 8 Airway oedema caused by microvascular leakage may contribute less in immature airways to airflow obstruction after SP or NKA.