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1Division of Pediatric Pulmonary Medicine, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and 2Division of Pulmonary Medicine, Department of Pediatrics, University of Texas Houston Medical School, Houston, Texas
Submitted 16 October 2006 ; accepted in final form 3 May 2007
Maturational changes have been noted in neurally mediated contractile and relaxant responses in airways from New Zealand White rabbits. In this study, we focused on prostaglandins with bronchoprotective properties as potential modulators of airway tone in maturing rabbits. Tracheal rings from 1-, 2-, and 13-wk-old rabbits were assessed for neurally mediated contractile and relaxant responses produced by electrical field stimulation (EFS) of nerves in the presence and absence of the prostaglandin inhibitor, indomethacin (Indo). We also measured EFS-induced release of prostaglandin E2 (PGE2) and the stable metabolite of prostacyclin, 6-keto-prostaglandin F1
(6-keto-PGF1
). In the presence of Indo, EFS produced significant increases in contractile responses in segments from 1- and 2-wk-old animals but not in segments from 13-wk adult rabbits. Tracheal rings from 1- and 2-wk-old animals precontracted with neurokinin A (NKA) relaxed 100% in response to EFS when Indo was not in the bath. In rings from 13-wk-old animals, relaxation was 40%. With Indo, relaxation was abolished in 1-wk-old animals and reduced to 30% in the 2- and 13-wk-old groups. Buffer from baths collected after EFS had significant increases in PGE2 and 6-keto-PGF1
released from tissues from 1- vs. 2- and 13-wk-old animals. Dose response curves to PGE2 using tissues precontracted to NKA showed significant increases in relaxant responses in 1- and 2- vs. 13-wk-old rabbits. In rabbit airways, this study demonstrates enhanced modulation of airway tone by PGE2 and greater release of the bronchoprotective prostaglandins PGE2 and prostacyclin early in life.
airway development; bronchoprotection; prostacyclin; prostaglandin E2; relaxant responses of airways
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