POS-272 DIFFERENTIAL EFFECTS OF ENDOTHELIN ETA RECEPTOR BLOCKADE ON VASCULAR CALCIFICATION AND RENAL INJURY IN RATS WITH CHRONIC KIDNEY DISEASE

Abstract

Endothelin ETA receptor blockade has been shown to reduce arterial stiffness and calcification without affecting renal function in a rat model of chronic kidney disease (CKD). In the present study, we investigated the differential effects of ETAreceptor blockade on vascular calcification and renal injury in CKD rats. CKD was induced in Wistar rats by renal mass ablation. Then, vascular calcification was induced by mineral imbalance with a calcium/phosphate-rich diet and vitamin D supplementation (Ca/P/VitD). One group of CKD+Ca/P/VitD rats was given the ETAreceptor antagonist atrasentan (10 mg/kg/day) for 6 weeks. Hemodynamic parameters, including systolic blood pressure (SBP), pulse pressure (PP) and pulse wave velocity (PWV) were determined. The thoracic aorta and the remnant kidney were harvested to assess vascular calcification and remodeling, and renal injuries. As expected, CKD+Ca/P/VitD rats developed arterial medial calcification associated with increased PWV and PP, indicating enhanced arterial stiffness. Renal injuries were comprised of mild focal and segmental glomerular sclerosis, diffused tubular atrophy and cortical and medullary interstitial fibrosis and inflammation. Although ETA receptor blockade improved vascular stiffness and calcification, unexpectedly, atrasentan aggravated renal injuries, including the tubular atrophy and the interstitial fibrosis and inflammation. In this rat model of CKD with vascular calcification, ETA receptor blockade reduced vascular stiffness and calcification, did not improve renal function due to aggravation of renal histological injuries.