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 ETA_A and AT1_A, 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 ETA_A and AT1_A.