Abstract 627: Measuring Renal Oxygenation in a Mouse Model of Volume-Dependent Hypertension using BOLD MRI.

Abstract

Hypertension is closely associated with the progression of kidney damage and dysfunction. Tissue hypoxia in the hypertensive kidney contributes to the progression of kidney damage. Peroxisome proliferator activated receptor-α (PPAR-α) is a nuclear receptor that plays an important role in reducing volume-dependent hypertension. Previous reports demonstrate that a slow pressor dose of Angiotensin II (Ang II) is a model of volume-dependent hypertension. The goal of this study was to determine the role of PPAR-α on renal oxygenation using blood oxygen level-dependent (BOLD) MRI in a model of volume-dependent hypertension. Wild-type (WT) and PPAR-α knockout (KO) mice were imaged using a multiple gradient echo BOLD sequence (12 echoes from 3.2-54ms, TR=900ms) on a 9.4T MRI to measure functional changes in renal oxygenation. Imaging was performed during baseline, day 12 of Ang II (400 ng/kg/min), and 9 days after Ang II-treatment (recovery). T2* relaxation time was measured in the cortex and medulla of the kidney. Cortex T2* values were lower in KO vs WT during baseline (11.0 ± 1.1 ms vs 13.1 ± 1.5 ms), day 12 of Ang II (11.6 ±1.2 ms vs 16.2 ±1.5 ms) and 9 days after Ang II (12.5 ± 0.7 ms vs 15.2 ± 0.3 ms). Medulla T2* values were lower on day 12 of Ang II in KO (16.5 ± 2.5 ms) vs WT (20 ± 1.6 ms) mice. Medulla T2* values were similar between KO and WT mice during baseline and the recovery period. In KO and WT mice, cortex T2* values were lower than that of the medulla, indicative of different metabolic functions between the two tissues. PPAR-α plays an important role in blood pressure regulation and renal oxygenation in the cortex and medulla of the kidney during Ang II-induced hypertension. Hypertension is a risk factor for chronic kidney disease when untreated. BOLD MRI can aid in monitoring renal oxygenation changes during hypertension and determine therapeutic interventions in humans.