NO‐independent activation of soluble guanylate cyclase prevents disease progression in rats with 5/6 nephrectomy

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Abstract
1 Chronic renal disease is associated with oxidative stress, reduced nitric oxide (NO) availability and soluble guanylate cyclase (sGC) dysfunction. Recently, we discovered BAY 58‐2667, a compound activating heme‐deficient or oxidized sGC in a NO‐independent manner. 2 We assessed potential of BAY 58‐2667 in preventing cardiac and renal target organ damage in rats with 5/6 nephrectomy. 3 Male Wistar rats were allocated to three groups: 5/6 nephrectomy, 5/6 nephrectomy treated with BAY 58‐2667 and sham operation. Study period was 18 weeks: blood pressure and creatinine clearance were assessed repeatedly. At study end blood samples were taken and hearts and kidneys harvested for histological studies. 4 BAY 58‐2667 markedly lowered blood pressure in animals with 5/6 nephrectomy (untreated versus treated animals: 189±14 versus 146±11 mmHg, PBritish Journal of Pharmacology (2006) 148, 853–859. doi:10.1038/sj.bjp.0706792