REN and Hypertension: Since hypertension and inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) are considered as risk factors for the development of chemotherapy-induced cardiotoxicity, cardiomyopathy and ultimately chemotherapy-induced HF [11,15], we decided to explore the characteristics of the DOX-induced model of HF in Ren-2 transgenic rats (TGR), in which the endogenous activation of the RAAS and hypertension are combined [33,36,37], and to compare them with those of normotensive transgene-negative, Hannover Sprague-Dawley (HanSD) rats.