Aim: Airway hyperresponsiveness is a constant feature of asthma.
The aim of the present study was to investigate airway hyperreactivity mediated by contractile and dilative receptors in an ovalbumin (OVA)-induced model of rat asthma.
Methods: Asthmatic E3
rats were prepared by intraperitoneal injection with
OVA/aluminum hydroxide and then challenged with intranasal instillation of
OVA-PBS two weeks later. The myograph method was used
to measure the responses of constriction and dilatation in the trachea, main
bronchi and lobar bronchi.
Results: In asthmatic E3 rats, β2 adrenoceptor-mediated
relaxation of airway smooth muscle pre-contracted with 5-HT was inhibited, and
there were no obvious difference in relaxation compared with normal E3 rats.
Contraction of lobar bronchi mediated by 5-HT and sarafotoxin
6c
was more potent than in the
trachea or main bronchi. Airway contractions mediated by the endothelin (ET)A receptor, ETB receptor and M3 muscarinic receptor were augmented, and the augmented contraction was most obvious in
lobar bronchi. The order of efficacy of contraction for lobar bronchi induced
by agonists was ET-1, sarafotoxin
6c
>ACh>5-HT.
OX8 (an antibody against CD8+ T cells) strongly shifted and OX35 (an
antibody against CD4+ T cells) modestly shifted isoprenaline-induced
concentration-relaxation curves in a nonparallel fashion to the left with an
increased Rmax in asthmatic rats
and sarafotoxin
6c
-induced concentration-contractile curves to the
right with a decreased Emax.
Conclusion: The
inhibition of airway relaxation and the augmentation of contraction mediated by
receptors contribute to airway hyperresponsiveness and involve CD8+ and CD4+ T cells.
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