Fig 2: ET-1-mediated vasoconstriction, contribution of ETB to ET-1-mediated response and coronary tissue levels of ET-1 and ETB in 4-month-old male and female offspring. (i) ET-1-mediated vasoconstriction in the presence or absence of (a) BQ123 (a competitive antagonist of ETA) or (b) BQ788 (a selective ETB receptors antagonist) in left descending coronary arteries of Normoxia (red) and p-Hypoxia (blue) male (A; circles) and female (B; squares) 4-month-old offspring. (ii) Data are summarized as area under the curve (AUC); n = 4–9 dams/group. (c) Representative confocal images of (i) ET-1 (green), (ii) ETA (green) and (iii) ETB (green) co-stained with CD31 (endothelial cell marker; red) and quantitative analysis of immunofluorescence staining in Normoxia (red symbol) and p-Hypoxia (blue symbol) male (circles) and female (squares) offspring; n = 4–6 dams/group. Data are presented as mean ± SEM; analyzed by t-test or two-way ANOVA with Sidak’s multiple comparison post-hoc test, ** p < 0.01, **** p < 0.0001.

Fig 3: ET-1-mediated vasoconstriction, contribution of ETB to ET-1-mediated response and coronary tissue levels of ET-1 and ETB in 9.5-month-old male and female offspring. ET-1-mediated vasoconstriction in the presence or absence of (a) BQ123 (a competitive antagonist of ETA) or (b) BQ788 (a selective ETB receptors antagonist) in left descending coronary arteries of Normoxia (red) and p-Hypoxia (blue) male (A; circles) and female (B; squares) 9.5-month-old offspring. (ii) Data are summarized as area under the curve (AUC); n = 5–8 dams/group. (c) Representative confocal images of (i) ET-1 (green), (ii) ETA (green), and (iii) ETB (green) co-stained with CD31 (endothelial cell marker; red) and quantitative analysis of immunofluorescence staining in Normoxia (red symbol) and p-Hypoxia (blue symbol) male (circles) and female (squares) offspring; n = 5–6 dams/group. Data are presented as mean ± SEM; analyzed by t-test or by two-way ANOVA with Sidak’s multiple comparison post-hoc test, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.