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

Fig. 3.

Fig. 3.

Potent VEGFR2 inhibitors do not induce PH in rats even in combination with hypoxia. (A) Western blotting of pVEGFR2 and total VEGFR2 (Left) and quantification of pVEGFR2 (Right). SU5416, Ki8751, and TAK-593, but not FICZ and indirubin, inhibited phosphorylation of VEGFR2 by VEGFA. (B) Experimental protocol for comparing the effect of Ki8751 and TAK-593 treatment with that of SU5416, in combination with hypoxia in rats. SU5416, Ki8751, TAK-593, or vehicle was subcutaneously administered once on day 0. (C and D) Assessment of SuHx, Ki8751/Hx/Nx, and TAK-593/Hx/Nx rats (Veh/Hx/Nx: n = 6, SuHx: n = 4, Ki8751/Hx/Nx: n = 3, TAK-593/Hx/Nx: n = 3). RVSP (C), Fulton’s index (D). (E) Representative images of distal acinar arterioles in lung sections of SuHx, Ki8751/Hx/Nx, or TAK-593/Hx/Nx rats subjected to EVG staining. (Scale bar, 30 μm.) (F) Medial wall thickness index of rats in E (Veh/Hx/Nx: n = 6, SuHx: n = 4, Ki8751/Hx/Nx: n = 3, TAK-593/Hx/Nx: n = 3). (G and H) Percentages of open, partial, and closed pulmonary arteries with OD < 50 μm (G) and OD: 50–100 μm (H) of rats in E (Veh/Hx/Nx: n = 6, SuHx: n = 4, Ki8751/Hx/Nx: n = 3, TAK-593/Hx/Nx: n = 3). Values are means ± SD; ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05.