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. 2021 Aug 6;8:680775. doi: 10.3389/fcvm.2021.680775

Figure 4.

Figure 4

Vascular effects of different Rac1 inhibitors: GTPase activity, oxidative stress and endothelial function. To investigate the vascular effects of different Rac1 GTPase inhibitors, ApoE−/− mice were fed a cholesterol-rich diet for 7 weeks and were concomitantly treated with vehicle, LT (0.1 μg LT/week), NSC 23766 (10 mg/kg/d), or simvastatin (20 mg activated simvastatin/kg/d). All three compounds significantly inhibited aortic Rac1 GTPase activity (A, Rac1 GTPase activity G-LISA, *p < 0.05 vs. vehicle, n = 4–7 per group), but only simvastatin significantly decreased aortic rhoA GTPase activity (B, rhoA GTPase activity G-LISA, *p < 0.05 vs. vehicle, n = 5–8 per group). All three compounds significantly reduced aortic NADPH oxidase activity (C, lucigenin-enhanced chemiluminescence, *p < 0.05 vs. vehicle, n = 3–5 per group) and aortic ROS production (D, L-012 chemiluminescence, *p < 0.05 vs. vehicle, n = 6–9 per group) and significantly improved endothelium-dependent vasodilation (E, organ chamber experiments with isolated aortic segments, *p < 0.05 vs. vehicle, n = 5 per group) compared to vehicle-controls. Endothelium-independent vasodilation was not affected by the Rac1 inhibitors (F, n = 5 per group).