P144 IMPACT OF ANTI-HYPERTENSIVE DRUGS ON AORTIC STIFFNESS INDUCED BY CHRONIC KIDNEY DISEASE AND MINERAL BONE DISORDER IN RATS

Abstract

Background: In chronic kidney disease (CKD), anomalies of mineral bone disorder (MBD) play a central role in vascular calcification and increased aortic stiffness. The impact of antihypertensive drugs on MBD-induced vascular calcification remains uncertain. The aim of this study was to examine whether endothelin A receptor antagonist (ETAA), angiotensin type-1 receptor antagonist (AT1A) and the combination of hydralazine/hydrochlorothiazide (HDZ/HCT) can reduce vascular stiffness in a rat model of CKD-MBD. Method: Using a remnant kidney model of CKD in rats, vascular calcification was induced by creating MBD through high a calcium-phosphate diet and vitamin D supplementation. Three antihypertensive treatments were investigated: atrasentan (ETA blocker), losartan (AT1 blocker) and HDZ/HCT. Blood pressures (BPs) were measured invasively after (6 weeks) and aortic stiffness was determined by the assessment of pulse wave velocity (PWV). Results: PWV and mean BP increased in rats with CKD-MBD as compared to CKD (640 ± 130 vs. 390 ± 34 cm/s and 100 ± 17 vs. 92 ± 21 mmHg; p p < 0.05). Treatment of CKD-MBD rats with ETAA and AT1A, but not HDZ/HCT, reduced PWV (517 ± 94, 596 ± 134 and 761 ± 116 cm/s respectively) despite similar reduction of mean BP by the different treatments (73 ± 16, 75 ± 19 and 70 ± 20 mmHg, respectively). Creatinine clearance and mineral metabolism parameters were relatively similar among groups. Conclusion: MBD-induced aortic stiffness in CKD rats was improved by atrasentan and losartan, but not the combination of HDZ/HCT, indicating blood pressure-independent protective effects of ETAA and AT1A.