Skip to main content
. 2022 Jul 1;132(13):e149117. doi: 10.1172/JCI149117

Figure 7. Functional role of Nox4 and Rho kinase in the regulation of vascular dysfunction by docetaxel in vivo.

Figure 7

(A) Schematic of the study design for WT mice injected with vehicle, docetaxel (10 mg/kg every 5 days), or docetaxel plus the Nox1/4 inhibitor GKT137831 (40 mg/kg every day) or placebo (solvent) for 3 weeks. (B) Systolic blood pressure by tail-cuff plethysmography (n = 6–7/group). Data are expressed as the mean ± SEM. #P < 0.01 versus baseline; **P < 0.01 versus WT (vehicle + placebo); ***P < 0.001 versus WT treated with docetaxel plus GKT137831; 2-way, repeated-measures ANOVA with Tukey’s test. (C) Endothelium-dependent vasorelaxation responses to ACh (1 nM–10 μM) and endothelium-independent vasorelaxation responses to SNP (1 nM–10 μM) in mouse aortas (n = 5–6/group). Data are expressed as the mean ± SEM. *P < 0.05 versus WT treated with docetaxel plus GKT137831; **P < 0.01 versus WT; 2-way, repeated-measures ANOVA with Tukey’s test. (D) Study design, for WT mice injected with docetaxel (10 mg/kg every 5 days) or docetaxel (10 mg/kg every 5 days) and the ROCK inhibitor fasudil (30 mg/kg every day) or placebo (solvent) for 3 weeks. (E) BP was measured by tail-cuff plethysmography (n = 6–7/group). Data are expressed as the mean ± SEM. #P < 0.01 versus baseline; ***P < 0.01 versus WT mice and WT mice treated with docetaxel plus fasudil; 2-way, repeated-measures ANOVA with Tukey’s test. (F) Endothelium-dependent vasorelaxation responses to ACh (1 nM–10 μM) and endothelium-independent vasorelaxation responses to SNP (1 nM–10 μM) in mouse aortas (n = 6/group). Data are expressed as the mean ± SEM. *P < 0.05 versus WT and WT mice treated with docetaxel plus fasudil; 2-way, repeated-measures ANOVA with Tukey’s test. (G) Effect of fasudil on phosphorylation of eNos at Thr495 in WT mice treated with docetaxel (n = 6/group). Densitometric analysis of proteins normalized to total eNos expression. Immunoblots are from 1 of 2 independent experiments. Data are expressed as the mean ± SEM. *P < 0.05 versus WT; **P < 0.01 versus WT mice treated with docetaxel plus fasudil; 1-way ANOVA with Tukey’s test.