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. 2024 Jul 8;16(8):1930–1956. doi: 10.1038/s44321-024-00096-0

Figure 5. FR induces pulmonary vasorelaxation in small PAs of mice and humans ex vivo and acutely reduces RVSP in PH mice in vivo.

Figure 5

(A, B) Phase contrast microscopy pictures of intrapulmonary mouse vessels after solvent DMSO (A) or FR (10−6 M) (B) application. Numbers indicate time points shown in the graph (1–3), scale bar: 20 μm. (C) Statistical analysis of small intrapulmonary vessel relaxation evoked by DMSO (n = 8 intrapulmonary PAs) or FR (10−6 M, n = 7 intrapulmonary PAs). (D, E) Phase contrast microscopy pictures of intrapulmonary vessels after solvent DMSO (D) or FR (10−6 M, E) application in precision-cut lung slices of human subjects, arrows indicate PAs, scale bar: 200 µm. (F) Statistical analysis of vascular area changes evoked by DMSO (n = 5 intrapulmonary PAs) or FR (10−6 M, n = 8 intrapulmonary PAs). (G) Original traces of PAP in the IPL mouse model during perfusion with 5-HT (10−6 M) and DMSO or FR (10−6 M). (H) Statistical analysis of DMSO (n = 6 mice) or FR (10−6 M, n = 6 mice)-induced PAP decrease. (I) Statistical analysis of 5-HT (5 × 10−7 M)-induced constriction amplitude in healthy mice housed under Nx (21% O2, n = 22) conditions or mice with Hx-induced PH (n = 12). (J) Statistical analysis of DMSO (n = 6) or FR (10−6 M, n = 6)-dependent pulmonary vasorelaxation after constriction with 5-HT (5 × 10−7 M) in mice with pre-existing Hx-induced PH. (K) Schematic diagram of the procedure for acute FR application and hemodynamic analysis in mouse in vivo. (L) Statistical analysis of basal RVSP 1 h after DMSO (n = 9) or FR (2.5 µg/mouse, n = 8) i.t. application in mice with pre-existing Hx-induced PH. (M) Statistical analysis of right ventricular pressure response to acute 5-HT i.v. bolus injection (5 × 10−3 M, 10 µl) in these mice (DMSO: n = 9; FR: n = 8). Data information: Values are expressed as mean ± SEM. (C, F, H, I, J, L, M) Unpaired student’s t-test. Source data are available online for this figure.