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Figure 2 Microphotographs of left ventricular myocardium stained with the collagen-specific dye Sirius red. Collagen fibers appear as red structures, and myocytes and intramyocardial vessels are yellow (magnification x40). A diffuse interstitial and a marked perivascular fibrosis is evident in placebo-treated eight-week-old TGRen2 (A). Irbesartan (B) and bosentan (C) treatment for four weeks resulted in a marked reduction of fibrosis, both in the interstitium and perivascularly. No effect of treatment with the ET_A receptor antagonist BMS-182874 (D) was seen. The combined treatment with irbesartan plus BMS-182874 (E) did not reduce cardiac fibrosis compared with placebo and with BMS-182874 alone.