The Endothelin Receptor Antagonist Macitentan Improves Isosorbide-5-Mononitrate (ISMN) and Isosorbide Dinitrate (ISDN) Induced Endothelial Dysfunction, Oxidative Stress, and Vascular Inflammation

Figure 8

Characterization of vascular function and oxidative stress and protective effects of macitentan cotherapy in ISDN-treated mice. Endothelium-dependent relaxation (ACh) was determined by isometric tension studies in aortic ring segments in order to assess endothelial function (a). Endothelium-independent relaxation (ISDN, GTN) was determined by isometric tension studies in aortic ring segments in order to measure nitrate tolerance and cross-tolerance (b, c). DHE (1 μM) oxidative fluorescence microtopography was used to assess vascular oxidative stress (d). Representative staining images are shown below the densitometric quantification, and the green fluorescence represents autofluorescence of the cytoplasmic membranes. The data are mean ± SEM from aortic ring segments of 10-12 (a, b, c) and 12 (d) mice per group. vs. control; vs. ISDN group.

(a)

(b)

(c)

(d)