We investigated the impact of respiratory syncytial virus(RSV) infection, an important asthma precipitant, on endothelinreceptor function and release in sheep bronchial explants. RSVinfection was confirmed using polymerase chain reaction andimmunohistochemistry. Since sheep airway smooth muscle containsonly endothelin-A receptors, sarafotoxin (Stx) S6c did not causeairway contraction. In contrast, sarafotoxin S6c (300 nM) causedcontraction in RSV-infected bronchial explants (8 ± 3% carbacholEmax). However, we could not detect airway smooth muscleendothelin-B receptors in explants using autoradiography. RSVinfection per se did not alter the release of immunoreactiveendothelin from sheep bronchial explants (control = 11.6 ± 0.9 pgversus RSV = 12.1 ± 0.9 pg). Interestingly, dexamethasone (1 μM)alone increased endothelin release in both control (17.9 ± 2.0 pg)and RSV-infected tissue (18.3 ± 3.1 pg). The combined presence ofprotease-activated receptor-2 (PAR-2) ligand (100 μM) anddexamethasone (1 μM) also increased endothelin release fromcontrol tissue (17.3 ± 1.4 pg), but endothelin release was suppressedby PAR-2 ligand in RSV-infected tissue (10.3 ± 0.8 pg), probablybecause PAR-2 expression was increased by RSV. In summary, thenovel expression of endothelin-B receptors triggered by RSV mightbe relevant to RSV-associated asthma. Furthermore, activation ofairway PAR-2 may be protective in asthma where endothelin levelsare elevated in part via endothelin release suppression.
|Journal||Journal of Cardiovascular Pharmacology|
|Issue number||Suppl 1|
|Publication status||Published - 2004|