Fig. 4. Local application of FR provides prolonged protection against Gq-dependent airway constriction in normal and OVA-sensitized mice in vivo. Local.

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Fig. 4. Local application of FR provides prolonged protection against Gq-dependent airway constriction in normal and OVA-sensitized mice in vivo. Local application of FR provides prolonged protection against Gq-dependent airway constriction in normal and OVA-sensitized mice in vivo. (A) Dose-response curves of respiratory system resistance (Rrs) in response to methacholine after inhalation of FR, salbutamol, or vehicle in healthy CD1 wild-type mice. (B) Dose-response curves for respiratory system resistance in response to methacholine treatment 24 hours after intratracheal application of FR in healthy CD1 wild-type mice. (C) Systemic systolic blood pressure (P) in healthy CD1 wild-type mice before (−) and 1 or 10 min after (+) inhalation of 2.5 μg of FR, control solution, or 5 μmol of the NO donor SNAP. (Note that 2.5 μg of FR was the amount that was used for aerosol application and that reduced respiratory system resistance.) (D) Systemic systolic blood pressure in healthy CD1 wild-type mice before (−) and after (+) intravenous injection of 2.5 or 12.5 μg of FR. (E) Tissue and plasma concentrations of FR 10 min after inhalation of 2.5 μg of FR by healthy CD1 wild-type mice. (F) Methacholine dose-response curves for respiratory system resistance after inhalation of vehicle or FR by OVA-treated Balb/c mice. *P < 0.05, **P < 0.01, ***P < 0.001. (A, B, and F) Two-way ANOVA, Bonferroni’s multiple comparison test. (C and E) One-way ANOVA, Tukey’s multiple comparison test (FR, control). (C and D) Paired two-tailed t test (SNAP). *P < 0.05, **P < 0.01, ***P < 0.001 FR versus control (A, B, and F), +P < 0.05 (FR versus salbutamol), ###P < 0.001 (salbutamol versus control). Michaela Matthey et al., Sci Transl Med 2017;9:eaag2288 Published by AAAS