Airway endothelin levels in asthma: influence of endobronchial hypertonic saline challenge.
BACKGROUND
The pathophysiology of exercise-induced asthma is not well understood. Hypertonicity of the airway lining fluid resulting from loss of water due to hyperventilation is considered to play a role, but the precise mechanism by which hypertonicity can induce bronchoconstriction is unknown. Peptides of the endothelin (ET) family have potent smooth muscle contractile properties, and have been linked to airway narrowing in stable asthma. We postulated that ET release may contribute to the acute bronchoconstrictor response induced by a hypertonic stimulus.


METHODS
Seven male asthmatic subjects underwent local endobronchial challenge with hypertonic (3.6%) saline and, as a control, isotonic (0.9%) saline aerosols in separate bronchopulmonary segments. Bronchoalveolar lavage (BAL) was performed at both sites during the phase of immediate bronchoconstriction. Concentrations of immunoreactive ET and of the mast cell products, histamine, tryptase and prostaglandin D2, in BAL fluid were measured.


RESULTS
Concentrations of ET in BAL fluid from the hypertonic saline-challenged sites were significantly lower than those in BAL fluid from sites exposed to isotonic saline (0.19 [0.11-1.24] fmol/mL vs. 0.40 [0.20-2.36] fmol/mL, P<0.05). Concentrations of histamine, tryptase, and prostaglandin D2 did not differ significantly between the two sites.


CONCLUSIONS
These findings do not support the hypothesis that ET release within the airway lumen is involved in the bronchoconstrictor response induced by hypertonic saline.
University Medicine, Southampton General Hospital, UK.
H K
HK
Makker
D R
DR
Springall
A E
AE
Redington
M A
MA
Ghatei
S R
SR
Bloom
J M
JM
Polak
P H
PH
Howarth
S T
ST
Holgate
D000328:Adult; D001250:Asthma, Exercise-Induced / Q000378:metabolism*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction / Q000187:drug effects; D001999:Bronchoscopy; D053818:Chymases; D016232:Endothelins / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D015230:Prostaglandin D2 / Q000378:metabolism; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism; D053802:Tryptases
D016232:Endothelins; D012462:Saline Solution, Hypertonic; D006632:Histamine; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D015230:Prostaglandin D2