Alteration of airway responsiveness mediated by receptors in ovalbumin-induced asthmatic E3 rats

Abstract

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, β 2 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, ET B receptor and M 3 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 R max in asthmatic rats and sarafotoxin 6c-induced concentration-contractile curves to the right with a decreased E max . 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.

Rosiglitazone elicits in vitro relaxation in airways and precision cut lung slices from a mouse model of chronic allergic airways disease

“…This was consistent with its ability to overcome functional antagonism in maximally contracted trachea from naïve mice. Previous studies have shown reduced ␤-adrenoceptor-mediated relaxation in rat and guinea pig trachea after allergen challenge (4,5,21). However, we did not find evidence to support this, with partial relaxation to ISO maintained, although the level of precontraction to MCh was not significantly increased in this subset of OVA-challenged mice.…”

Allergic Sensitization Increases Contractile Responses to 5-HT in Guinea Pig Aorta

“…A number of inflammatory mediators have been proposed as being involved in the pathophysiology of asthma, but to date the role of 5-hydroxytryptamine (5-HT, serotonin) has been relatively poorly investigated. In animals, 5-HT induces airway smooth muscle contraction (Long et al 2009), blockade of the 5-HT 2A receptor by ketanserin decreases allergen-induced airway hyperreactivity (De Bie et al 1998), and plasma 5-HT levels are increased in sensitized animals compared with non-sensitized controls (Arreola-Ramirez et al Vol. 69 2013).…”

Dynamics of airway response in lung microsections: a tool for studying airway-extra cellular matrix interactions

“…The velocities of this constrictor response to challenge with acetylcholine (Ach), as well as the relaxant response to washing off of Ach, were both obtained by taking the first derivatives of the changes in airway diameter with respect to time [ 16 , 38 , 39 ]. It has been reported in various preclinical settings that challenge of the airway tissues with neurotransmitters (10 −5 to 10 −8 Acetylcholine, 10 −5 5- hydroxytryptamine or 5-HT) and/or relaxants (10 −6 M Isoproterenol) leads to changes in diameter of airways; these responses can be easily videotaped and analyzed using lung microsection techniques for magnitudes and velocities of contraction, both of which reflect changes in the interactions of the smooth muscle with the surrounding tissue [ 2 , 39 , 44 ]. In addition to this, various targets can be tested to assess the roles of inflammation, fibrosis, metalloproteinases and other parameters in these structural/functional changes [ 16 ].…”