REN and chronic kidney disease: To this end, runcaciguat was given as a chronic oral treatment to (a) a hypertensive model of CKD in angiotensin II-treated Sprague–Dawley rats (ANG-SD), (b) a hypertensive CKD model, the renin transgenic (RenTG) rat [TGR(mRenR2)27] (Mullins et al., 1990, Ganten et al., 1991), with further increased oxidative stress burden and endothelial dysfunction by chronically supplemented NO synthase inhibitor L-NAME, and (c) obese and diabetic Zucker diabetic fatty (ZDF) rats [(ZDF-Lebrfa-Crl)] also characterized by progressive loss of kidney function (Shiota and Printz, 2012).