Figure 2: Noradrenaline-driven fibrogenesis requires functional neurotransmitter receptors.

(A-D) Wild-type mice received orally administered terazosin, an α1-adrenoceptor antagonist, at 1 or 10 mg/kg, or a vehicle from Days 5 to 13 post-bleomycin challenge and were euthanized on Day 14. Terazosin dosed at 1 mg/kg reduced collagen accumulation (A, P = 0.0291) and trichome staining (B--D). (E-H) Treatment with atenolol, a β1-adrenoceptor antagonist, and ICI118,551, a β2-adrenoceptor antagonist, at 1 mg/kg intraperitoneally improved both collagen deposition (E, P = 0.0021; P = 0.0098, respectively) and trichrome staining (F-H). (I-L) Intraperitoneal injections of nisoxetine, a NAT antagonist, at 3 or 10 mg/kg did not reduce collagen accumulation (I) or improve trichrome staining (J-L). (M-O) Both wild-type (Slc6a2^+/+) and NAT-deficient (Slc6a2^−/−) mice were subjected to inhaled bleomycin without observing any protective effect against collagen accumulation in NAT-deficient mice (M) or improvement in trichrome staining (N, O). Images were captured at 20x magnification. Data are presented as mean ± SEM or median ± IQR. Statistical analyses were conducted using Student’s t-test or ANOVA with Tukey’s multiple comparisons for normally distributed data, and Kruskal-Wallis tests with Dunn’s multiple comparisons for non-normally distributed data. *P < 0.05, **P < 0.01. NAT, noradrenaline transporter; Slc6a2, solute carrier family 6 member 2.