The aim of the present study was to perform kidney messenger ribonucleic acid (mRNA) analysis in normotensive, Hannover Sprague-Dawley (HanSD) rats and hypertensive, Ren-2 renin transgenic rats (TGR) after doxorubicin-induced heart failure (HF) with specific focus on genes that are implicated in the pathophysiology of HF-associated cardiorenal syndrome. We found that in both strains renin and angiotensin-converting enzyme mRNA expressions were upregulated indicating that the vasoconstrictor axis of the renin-angiotensin system was activated. We found that pre-proendothelin-1, endothelin-converting enzyme type 1 and endothelin type A receptor mRNA expressions were upregulated in HanSD rats, but not in TGR, suggesting the activation of endothelin system in HanSD rats, but not in TGR. We found that mRNA expression of cytochrome P-450 subfamily 2C23 was downregulated in TGR and not in HanSD rats, suggesting the deficiency in the intrarenal cytochrome P450-dependent pathway of arachidonic acid metabolism in TGR. These results should be the basis for future studies evaluating the pathophysiology of cardiorenal syndrome secondary to chemotherapy-induced HF in order to potentially develop new therapeutic approaches.

Center for Experimental Medicine Institute for Clinical and Experimental Medicine 14021 Prague Czech Republic

Department of Cardiology Institute for Clinical and Experimental Medicine 14021 Prague Czech Republic

Department of Cardiology University Hospital Motol and 2nd Faculty of Medicine Charles University 15006 Prague Czech Republic

Department of Nephrology 1st Faculty of Medicine Charles University 12108 Prague Czech Republic

Department of Pathophysiology 2nd Faculty of Medicine Charles University 15006 Prague Czech Republic

Department of Renal and Body Fluid Physiology Mossakowski Medical Research Institute Polish Academy of Sciences PL02 106 Warsaw Poland

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Transgenic rat with ubiquitous expression of angiotensin-(1-7)-producing fusion protein: a new tool to study the role of protective arm of the renin-angiotensin system in the pathophysiology of cardio-renal diseases

Characterization of a new model of chemotherapy-induced heart failure with reduced ejection fraction and nephrotic syndrome in Ren-2 transgenic rats