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Ontogeny of epithelial modulation of airway smooth muscle function in the guinea pig
Author(s) -
Southgate W. Michael,
Pichoff Bruce E.,
Stevens Edward L.,
Balaraman Venkataraman,
Uyehara Catherine F. T.,
Nakamura Kenneth T.
Publication year - 1993
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.1950150207
Subject(s) - isometric exercise , fetus , histamine , guinea pig , acetylcholine , contraction (grammar) , endocrinology , medicine , respiratory epithelium , ontogeny , anatomy , respiratory system , biology , pregnancy , genetics
The purpose of this study was to investigate the ontogeny of guinea pig airway smooth muscle (ASM) responses and the epithelial modulation of these responses. Paired tracheal rings from fetal, newborn, and adult guinea pigs were studied. One of each pair was denuded of airway epithelium (AE) by gentle rubbing. Isometric tension was measured in rings mounted in organ baths filled with ‘Krebs’ solution. Cumulative dose‐response curves were generated by adding either acetylcholine (ACh) or histamine over a concentration range of 1 0 −8 −10 −4 M. Significant agent‐specific, age‐related differences in maximal contraction were seen for both ACh and histamine in intact tissues (Ach: for fetus 66.7 ± 6.2 × 10 −2 g/mg wet wt, for newborn 51.4 ± 6.2, for adult 29.3 ± 2.6; histamine: for fetus 46.1 ± 5.1, for newborn 72.9 ± 6.0, for adult 25.3 ± 3.2). Similar differences in sensitivity to both agents were observed (EC 50 with ACh: for fetus 0.80 ± 0.11×10 −6 M; for newborn 0.85 ± 0.26 × 10 −6 M; for adult 1.7 ± 0.20 × 10 −6 M; EC 50 with histamine: for fetus 1.88 ± 0.50 × 10 −6 M; for newborn 1.34 ± 0.16 × 10 −6 M; for adult 3.78 ± 0.75 × 10 −6 M). Removal of AE caused a significant decrease in maximal responses to ACh in fetal tissue, a smaller, insignificant one for newborn and a nonsignifcant alteration for adult tissues. Age‐related sensitivity difference was abolished with removal of AE to ACh but not to histamine. In conclusion, during development (1) maximum tension, expressed as force per tissue weight, when generated follows the pattern, fetus > newborn > adult with ACh and newborn > fetus > adult with histamine; (2) the EC 50 pattern for both ACh and histamine was, fetus = newborn < adult; (3) for denuded tissue maximum tension by ACh was significantly decreased only in fetal trachea; and (4) removal of AE abolished the age‐dependent difference in sensitivity to ACh, but not to histamine. © 1993 Wiley‐Liss, Inc.