Figure 4: Small molecule Hif2 inhibitor PT2567 significantly attenuates development of hypoxia-induced PH at 4 weeks in adult rats.
Sprague Dawley (SD) male rats weighing 210–245 grams (Charles River Laboratories) were housed in chambers under normoxia or hypoxic (high altitude ~ 18,000 feet) conditions for four weeks. Rats were dosed with vehicle methylcellulose (0.5%)/Tween-80 (0.5%) or PT2567 (300 mg/kg/day), beginning the day they were placed in chambers. After 4 weeks, endpoint measurements for the experimental animals were conducted (A–C). A) Mean Pulmonary Arterial Pressure. B) Ratio of weight of right ventricle versus weight of left ventricle. C) Representative images of pulmonary vessels stained with anti-macrophages/monocytes antibody, clone ED-1 (Top), anti-Ki67 antibody (Middle), or anti-Tenascin C antibody (Bottom). The levels of CD68, CCNA1, and TNC mRNAs in the whole lung tissues of indicated rats were also shown (Right). D, E) α-SM-actin positive pulmonary vessels, scale bar: 100μm. Statistical significance determined by 2-way ANOVA (A, B) or by t-test (C–E).