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Figure 1 Midostaurin reduces aortic production of reactive oxygen species and reverses endothelial-type nitric oxide synthase (eNOS) uncoupling in spontaneously hypertensive rats (SHR). Aortas were isolated from SHR or Wistar-Kyoyo (WKY ) rats treated orally with vehicle or midostaurin (+Mido, 75 mg/kg/day for 5 days). Production of reactive oxygen species (ROS) from aortic rings (3 mm) was determined by L-012–derived chemiluminescence in the absence or presence of the NOS inhibitor L-NAME (1 mmol/l) (A). Each column represents ROS determinations (mean ± SEM) obtained with aortas from six different animals (**p < 0.01 compared with any other column, tested by analysis of variance (ANOVA) followed by Fisher protected least-significant-difference test). (B) ROS production in SHR aorta as detected with fluorescent microscopy using dihydroethidium. Aortas were incubated with or without L-NAME (1 mmol/l) and then labeled with dihydroethidium, which produces a red fluorescence when oxidized to ethidium by superoxide. The autofluorescence of the elastic laminae is in green. Arrows indicate the endothelium.
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