Hypertensive organ injury on the basic of 5/6 nephrectomy in REN2 transgenic rats

Hypertension is a major determinant of rate of progression of CKD. Treatment of systemic hypertension is now generally accepted as the most important clinical strategy to slow the progression of CKD to ESRD. Renin-angiotensin (RAS) and endothelin (ET) systems are important contributors to the pathogenesis of hypertension. The interaction between the RAS and ET systems also plays a crucial role in the development of hypertension- associated end-organ damage. Antihypertensive drugs that block the renin-angiotensin system (RAS) are now believed to provide class- specific renoprotective actions beyond their blood pressure lowering effects. Our first study was performed to compare the organ-protective effects of a RAS-dependent and a RAS-independent antihypertensive therapy in heterozygous (mRen-2)27 transgenic rats (TGR) after 5/6 renal ablation (5/6 NX). Normotensive transgene-negative Hannover Sprague-Dawley (HanSD) rats after 5/6 NX served as controls. RAS-dependent and -independent antihypertensive therapies induced equal reductions of BP and almost identical cardio- and renoprotective effects on the progression of CKD after 5/6 NX, in both HanSD and TGR. These findings suggest that the cardio- and reno-protection, at least in rats after 5/6 NX, is mainly mediated through BP- dependent mechanisms...