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Evidence for interaction between endothelin receptors in equine airways
Author(s) -
Venugopal Changaram,
Mariappan Nithya,
Koch Catherine,
Holmes Earnestine
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.931.3
Subject(s) - chemistry , antagonist , receptor , endothelin receptor , contraction (grammar) , blockade , superoxide , endocrinology , reactive oxygen species , medicine , receptor antagonist , endothelin 1 , pharmacology , biochemistry , enzyme
Endothelin‐1 (ET), an inflammatory mediator, causes potent contraction of airway smooth muscles leading to oxidative stress (OS) by binding to ETA and ETB receptors. We investigated the interaction between the ETA and ETB receptors in contractions and OS on healthy equine bronchial rings. Rings were prepared from right diaphragmatic lobe. Rings for response studies were set in the tissue chambers containing oxygenated Tyrode's solution at 37 o C and 2‐gm tension was applied. Concentration‐response relationships were determined with graded concentrations of ET‐1 on control rings, rings incubated with ETA and ETB antagonists, separately and combined. For OS studies, each ring was incubated for 30 min separately with ET, ET+ETA antagonist, ET+ ETB antagonist and ET+ ETA+ETB antagonists. Total reactive oxygen species (ROS), superoxide production and peroxynitrate were determined using Brucker EMX ESR spectrophotometer. ET caused dose‐dependent contraction which was enhanced by ETA blockade and was decreased by ETB blockade. Combined blockade significantly inhibited the response by ET. ET‐induced total ROS was decreased in all treatments. Superoxide production was slightly decreased by antagonists individually but increased when combined. Peroxynitrate production was increased by ETA antagonist, but decreased in other treatments. The study suggested that an interaction between ET‐receptors exists both in contractile response and OS. Supported by USDA Formula Funds (# LA 1433) and EHSP of LSU‐SVM.