A15194 INVOLVEMENT OF ENDOTHELIN AND ANGIOTENSIN II IN CHRONIC KIDNEY DISEASE-RELATED ARTERIAL STIFFNESS

Abstract

Objectives: Increased risk of cardiovascular disease in patients with chronic kidney disease (CKD) has been related to vascular stiffness and isolated systolic hypertension. Using a rat model of CKD with mineral imbalance, we reported that endothelin (ET)A receptor blockade reduced vascular stiffness and hypertension revealing a role for endothelin. This study was designed to investigate whether the protective effect of ETA receptor blockade on vascular stiffness is independent of blood pressure reduction. Methods: CKD was induced in Wistar rats by renal mass ablation and mineral imbalance by a calcium/phosphate-rich diet and vitamin D supplementation (Ca/P/VitD) which increased vascular stiffness. CKD rats given Ca/P/VitD were treated either with the ETA receptor antagonist atrasentan (10 mg/kg/d), the angiotensin AT1 receptor antagonist losartan (25 mg/kg/d) or the combination of hydrochlorothiazide/hydralazine (Hy/Hy; 100 mg/L and 25 mg/L, respectively) for 5 weeks. Hemodynamic parameters were determined by vessels catheterisation in anesthetised animals. Results: Systolic blood pressure and carotid-femoral pulse wave velocity were higher in CKD+Ca/P/VitD rats as compared to CKD control (p < 0.05). Treatment of CKD+Ca/P/VitD rats with atrasentan, losartan and Hy/Hy reduced mean, diastolic and systolic blood pressure (p < 0.05). However, treatment with atrasentan and losartan, but not Hy/Hy, reduced carotid-femoral pulse wave velocity (p < 0.05). Conclusion: The protective effect of ETA and AT1 receptor blockade on vascular stiffness is independent of the blood pressure lowering effect in CKD rats with mineral imbalance. This study reveals a role for both endothéline and angiotensin II in CKD-related vascular stiffness.