Fig. 6 | Nature Communications

Fig. 6

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

Fig. 6

Bradykinin-induced bronchoconstriction in ovalbumin-sensitized rats is dependent on the carotid body and LPA signaling. a OVA-sensitization protocol (see Methods, OVA Cohort 2) to test lung–carotid body–lung pathway. b OVA-sensitized and naive rats were exposed to nebulized saline (baseline) and three consecutive nebulizations of 0.4 mg bradykinin at 1 (solid), 10 (hatched), and 20 (crossed) min while measuring RL. Bradykinin had group specific effects: See Methods, OVA Cohort 2; F14,143 (two-way RM ANOVA: time × group) = 4.035, p < 0.001. Holm–Šidák post hoc: bradykinin caused a marked increase in RL in OVA-sensitized (red; **p < 0.01) but not naive rats (white; p > 0.3) rats; carotid body (CB) denervated (blue), vagi (VaG) denervated (purple), TRPV1 blockade (AMG9810, orange), LPAr blockade (BrP-LPA, yellow and Ki16425, fuscia) and dual TRPV1 and LPAr blockade (AMG9810 + BrP-LPA, green), abolished the effects of bradykinin compared to OVA (Holm–Šidák post hoc: *p < 0.05; ***p < 0.001). c Chronic CB denervation (blue; but not sham-treatment, red) also abolished bradykinin-induced bronchoconstriction in OVA-sensitized animals (see Methods OVA Cohort 3; F2,32 (two-way RM ANOVA time × group) = 5.418, p = 0.014; Holm–Šidák post hoc: Intact greater than denervated, 10 and 20 min greater than 1 min in Intact, **p < 0.01). d Bronchoconstriction in response to capsaicin does not involve the carotid body (see Methods OVA Cohort 4). RL was measured 2 and 10 min after single capsaicin nebulization in OVA (red) and naive (gray) rats who had intact (solid) or resected vagi (hatched). All rats had denervated carotid bodies yet all, including naive animals, exhibited bronchoconstriction in response to capsaicin by 2 min (F3,47 (two-way RM ANOVA treatment × group) = 8.435, p < 0.001). Holm–Šidák post hoc: capsaicin-induced bronchoconstriction was abolished by vagotomy: ***p < 0.001; different between 2 min and 10 min ***p < 0.001; **p = 0.002. In bd, RL is normalized to that during initial saline nebulization. All data are presented as mean ± sem