(A) Experimental approach. (B) 5-HT2B antagonist, SB204741, normalizes RVSP in mice exposed to hypoxia+SU5416. This effect is not observed in animals exposed to hypoxia alone. (C) SB204741 has no effect on RV remodeling in either animal model (n=7–8). (D-E) Animals exposed to hypoxia+SU5416 have significantly more muscularized arterioles (< 100 μm diameter) than animals exposed to hypoxia alone, and SB204741 significantly reduces the number of fully muscularized arterioles in hypoxia+SU5416 exposed but not in hypoxia alone exposed animals (n=3–5). (F) SB204741 normalizes arteriole stiffness in animals exposed to hypoxia+SU5416, but not in animals exposed to hypoxia alone (n=3–6). (G) Representative modulus distributions and (H) scan windows for individual vessels. (B-D, F) Mean +/−S.E., n.s. = not significant, *p<0.05 following (B,C,F) 2-way ANOVA and Holm-Sidak post-hoc test or (D) Kruskal-Wallis rank sum test with Conover-Iman post-hoc test.