sGC stimulator BAY 41‐8543 improves survival and ventricular function in a rat model of doxorubicin‐induced cardiomyopathy with nephrotic syndrome

BACKGROUND AND PURPOSE: Anthracyclines such as doxorubicin (DOXO) remain a cornerstone of cancer therapy but are associated with a high risk of cardiotoxicity and subsequent heart failure (HF). Impairment of NO/soluble guanylyl cyclase (sGC)/cGMP pathway has been reported in anthracycline-induced cardiomyopathy. This raises the hypothesis that increasing cGMP by sGC stimulation could preserve cardiac function even after HF has developed. This study aimed to evaluate the long-term effects of treatment with sGC stimulator BAY 41-8543 in a model of DOXO-induced HF with nephrotic syndrome in hypertensive rats. EXPERIMENTAL APPROACH: ). Echocardiography, blood and urine collection were performed at baseline (week -1) and 4 weeks after the treatment started to assess cardiac ventricular function, cardiac and renal biomarkers; survival at 20 weeks. KEY RESULTS: Treatment with BAY 41-8543 improved long-term survival, preserved left and right ventricular systolic function and reduced myocardial expression of inflammation-related genes, particularly those linked to type I interferon signalling. ACEi provided stronger benefits in survival and structural remodelling. Kidney damage and function was not improved by any treatment compared to placebo. CONCLUSION AND IMPLICATIONS: The sGC stimulator BAY 41-8543 exerted significant cardioprotective effects in DOXO-induced HF. Therefore, sGC stimulators may represent a promising therapeutic option for anthracycline-induced cardiomyopathy, although additional studies are required to fully investigate their therapeutic potential.