Figure 1. Ang II resistance characterizes normal pregnancy, while sFlt1 overexpression is sufficient to cause Ang II sensitivity.

(A) Blood pressure measurements in nonpregnant (n = 5) and pregnant CD-1 mice (n = 3) with Ang II infusion via s.c. osmotic minipump beginning on day 12. *P < 0.05 for mean arterial pressure (MAP) in pregnant mice versus nonpregnant mice. (B) MAP comparison between nonpregnant (n = 5) and pregnant mice (n = 3) infused with Ang II. ΔMAP was obtained by subtraction of individual pressure at day 17 from that at day 7. Day 7 was selected as the latest time point when all animals had no pressure differences (prior to intervention). *P < 0.001 by unpaired 2-tailed t test. (C) MAP of CMV-null (n = 5) and sFlt1-injected (n = 3) mice over gestation. Mice were injected at gd8 (arrow). MAP in sFlt1 mice was significantly increased relative to CMV-null and within-group baseline beginning at gd12; *P < 0.001. (D) Comparison of MAP between CMV-null mice (n = 5) and sFlt1 mice (n = 3). ΔMAP was obtained by subtraction of individual pressure at gd17 from that at gd7. *P < 0.01 by 1-way ANOVA and Bonferroni’s post-hoc test. (E) ΔMAP following acute i.v. Ang II bolus (30 ng in 30 μl saline plotted as medians (minimum and maximum), n = 3–5. ΔMAP was calculated by subtraction of individual data points from preinjection data (t = 0) for each animal every 5 minutes for 15 minutes following injection. Data were recorded as nonpregnant (NP), at increasing gestational days, and postpartum (PP). *P = 0.01 compared with NP and sFlt1 at gd14. (F) MAP of CMV-null (n = 3) and sFlt1-injected (n = 4) mice given chronic Ang II over gestation. Mice were injected with adenovirus at gd8 (arrow) and implanted with s.c. osmotic minipumps containing Ang II at gd12 (dashed line). *P < 0.01 for MAP in sFlt1 mice versus CMV-null mice. Data for CMV-null mice in this figure were obtained from data shown as the pregnant group in A. (G) Comparison of MAP between CMV-null (n = 3) and sFlt1 mice (n = 4) given chronic Ang II. ΔMAP was obtained by subtraction of individual pressure at gd17 from that at gd7. *P < 0.05 by 1-way ANOVA with Bonferroni’s post-hoc test. Data for the CMV-null mice in this figure were obtained from data shown as the pregnant group in B. (H) Contraction of ex vivo mesenteric resistance vessels in gd17 CMV-null or sFlt1 mice in response to Ang II or phenylephrine (n = 4 per group). *P < 0.05 by unpaired 2-tailed t test. Analyses used 2-way ANOVA with repeated measures, with the exception of B, D, G, and H, as indicated. All data represent the mean ± SEM, except in E.