PS-BPB05-2: ENDOTHELIN A RECEPTOR BLOCKADE INCREASES RENOPROTECTION IN EXPERIMENTAL MODEL OF CONGESTIVE HEART FAILURE COMBINED WITH CHRONIC KIDNEY DISEASE

Objective: Congestive heart failure (CHF) represents an extreme burden to the public healthcare worldwide. The incidence and prevalence of chronic kidney disease (CKD) is also increasing and CKD is known as one of the strongest risk factors for the development of CHF. CHF coexists with CKD in approximately half of CHF patients and results in a poor survival rate. The aim of this study was therefore to examine if the addition of endothelin type A (ETA) receptor antagonist atrasentan (5 mg/kg/day) to the angiotensin-converting enzyme inhibitor (ACEi trandolapril; 2 mg/L) will bring additional beneficial effects. Design and Methods: CKD was induced by 5/6 renal mass reduction (5/6 NX) at the age of 8 weeks and CHF was elicited by volume overload achieved by the creation of aortocaval fistula (ACF) four weeks later in normotensive Hannover Sprague Dawley rats. The follow-up was 24 weeks after the first intervention (5/6 NX). The treatment regimens were initiated 6 weeks after 5/6 NX and 2 weeks after ACF. Results: The final survival in untreated group was 15%. The treatment with ETA receptor antagonist alone or ACEi alone and the combined treatment improved the survival rate to 64%, 71% and 75%, respectively, with no significant difference between the combination and either single treatment regimen. At the end of the study, atrasentan or trandolapril given alone partially reduced albuminuria, but had no effect on albumin/creatinine ratio. In contrast, both parameters were substantially improved by the combined treatment which caused ∼45 % reduction in albuminuria. Moreover, it also reduced markers of renal damage. Conclusions: Our results demonstrated that the treatment with ETA receptor antagonist attenuated the mortality related to CKD or CHF and that the addition of ETA receptor antagonist to the standard blockade of renin angiotensin system by ACEi exhibited additional renoprotective actions.