Figure 1. Systemic NAC and SNOAC cause hypoxia-mimetic PAH in mice.
C57BL/6/129SvEv, C57BL/6, and eNOS–/– male mice were maintained in normoxia (N, red; 21% O2) or hypoxia (H, black; 10% O2); or were treated with NAC (blue) or SNOAC (green) in their drinking water for 3 weeks. (A) Relative RV weight was determined as the ratio of the weight of the RV to the LV+S weight. (B) RV systolic pressures were measured in the closed chest using a Millar 1.4 F catheter/transducer. (C) Representative RV pressure (RVP) tracings (each = 1 s). (D) Lung section images from C57BL/6/129SvEv mice immunostained for von Willebrand factor and α-SMA to illustrate changes in muscularization after 3 weeks of exposure to normoxia, hypoxia, NAC, or SNOAC. Scale bar: 100 μm (applies to all panels). (E) Changes in muscularization in C57BL/6/129SvEv mice in the small (<80-μm) vessels from histological sections (as in D) counted by an observer blinded to the protocol. FM, fully muscular; PM, partly muscular, NM, nonmuscular. Significant increases in muscularization in each treatment group were seen in comparison to normoxic controls. Data are mean ± SEM. ζP < 0.02, *P < 0.001, †P < 0.003, by 1-way ANOVA followed by pairwise comparison, all compared with normoxic control.