S-Nitrosothiols signal hypoxia-mimetic vascular pathology
J. Clin. Invest. Lisa A. Palmer, et al. 117:2592 doi:10.1172/JCI29444 [
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Figure 1Systemic 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% O
2) or hypoxia (H, black; 10% O
2); 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.
