Fig. 7 | Nature Communications

Fig. 7

From: Preventing acute asthmatic symptoms by targeting a neuronal mechanism involving carotid body lysophosphatidic acid receptors

Fig. 7

LPAr + TRPV1 blockade abates acute asthmatic respiratory distress in conscious rats. a OVA-sensitization protocol (see Methods, OVA Cohort 6). b, c Inspiratory:expiratory time decreased (Ti:Te; F35,431(two-way RM ANOVA time × group) = 8.577, p < 0.001, Holm–Šidák post hoc: p < 0.05, * different between groups at indicated time), expiratory time increased (Te; F35,431 (two-way RM ANOVA time × group) = 3.948, p < 0.001, Holm–Šidák post hoc: p < 0.05, * different between groups at indicated time) in response to acute OVA provocation following OVA sensitization, confirming these parameters as indices of acute asthmatic respiratory distress in conscious animals. d 21-Day sensitization protocol to test dual LPAr + TRPV1 blockade on respiratory distress (see Methods OVA Cohort 7); LPAr + TRPV1 blockade (T), vehicle (V), or saline (S; randomized) were delivered 20 min after the onset of OVA (as indicated by the arrows). e Decrease in Ti:Te and f increase in Te caused by allergen provocation are rescued by dual blockade (blue). Ti:Te: F70,1293 (two-way RM ANOVA group × time = 3.169, p < 0.001; Te: F35, 385 (two-way RM ANOVA time) = 10.590, p < 0.001, F2, 35 (two-way RM ANOVA group) = 7.393, p = 0.004). Holm–Šidák post hoc: dual block is significantly different from OVA-sensitized saline injected (red circles)* and vehicle injected (pale red triangles)^ groups, at indicated time points, p < 0.05. g The peak Ti:Te responses recorded 120 min after OVA exposure on day 21 in animals never having received dual blockade (red—from b), having dual blockade on day 21 and recorded on day 21 (acute treatment, light blue, from e), or having dual blockade on day 18 and recorded on day 21 (Long term treatment, dark blue, from e; F2,15 (one-way ANOVA group) = 45.805, p < 0.001). h The peak Te (120 min) response recorded on day 21 following OVA exposure; groups as per g. Dual antagonist injection on days 18 or 21 reduced respiratory indices of acute bronchoconstriction; and remarkably, dual antagonist injection on day 18 also had beneficial effects three days later, on day 21, without a subsequent dual antagonist injection (F2,15 one-way ANOVA group = 25.906, p < 0.001). Holm–Šidák post hoc: difference between indicated groups ***p < 0.001. Data are presented as mean ± sem

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