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. 2021 Mar 8;118(11):e2023899118. doi: 10.1073/pnas.2023899118

Fig. 2.

Fig. 2.

The endogenous AHR ligand FICZ induces severe PH in rats in combination with hypoxia. (A) Experimental protocol for determining whether FICZ treatment can induce PH in rats in combination with hypoxia (FICZ/Hx/Nx model). FICZ or vehicle was subcutaneously administered to rats every week. The rats were housed in a state of hypoxia (10% oxygen) for the first 3 wk, followed by normoxia for 2 or 5 wk. RHC: right heart catheterization. (B and C) Assessment of FICZ/Hx/Nx rats (Veh: vehicle, Hx: hypoxia, Nx: normoxia; normoxia: n = 5, Veh/Hx/Nx 5 wk: n = 7, FICZ/Hx/Nx 5 wk: n = 6, Veh/Hx/Nx 8 wk: n = 6, FICZ/Hx/Nx 8 wk: n = 7). RVSP (B), Fulton’s index (C). (D) Representative images of the vascular remodeling of distal acinar arterioles in lung sections subjected to Elastica van Gieson (EVG) staining in normoxia, Veh/Hx/Nx 5-wk, FICZ/Hx/Nx 5-wk, Veh/Hx/Nx 8-wk, and FICZ/Hx/Nx 8-wk rats. (Scale bar, 30 μm.) (E) Medial wall thickness index of FICZ/Hx/Nx rats (normoxia: n = 3, Veh/Hx/Nx 5 wk: n = 4, FICZ/Hx/Nx 5 wk: n = 3, Veh/Hx/Nx 8 wk: n = 6, FICZ/Hx/Nx 8 wk: n = 6). (F and G) Pulmonary arterial occlusions were graded as open (no luminal occlusion; green), partial (<50% occlusion; yellow), or closed (≥50% occlusion; red). Percentages of open, partial, and closed pulmonary arteries of outer diameter (OD) < 50 μm (F) and OD: 50–100 μm (G) in FICZ/Hx/Nx rats (normoxia: n = 3, Veh/Hx/Nx 5 wk: n = 4, FICZ/Hx/Nx 5 wk: n = 3, Veh/Hx/Nx 8 wk: n = 6, FICZ/Hx/Nx 8 wk: n = 6). Values are means ± SD; ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05.