Abstract 164: Disorder of Fatty Acid Oxidation in the Kidney of Rats With Angiotensin II-Induced Hypertension

Abstract

Abnormal lipid metabolism is common in patients with hypertension and chronic renal failure. Angiotensin II (Ang II) treatment causes high blood pressure and lipid accumulation in the kidney of rats. However, the mechanism of the Ang II-induced lipid accumulation in the kidney is not fully clarified. The present study was designed to examine changes of fatty acid metabolism in the kidney of Ang II-treated rats. Male Sprague-Dawley rats were treated with vehicle or Ang II (400ng/kg/min) by using osmotic mini-pumps for 7 days. The protein expression of enzymes associated with fatty acid metabolism in the kidney was analyzed by using immunoblot ananlysis. After 7 days, Ang II treatment significantly increased the systolic blood pressure (112.0±2.8mmHg versus 134.6±3.4mmHg; P<0.01) and urinary albumin excretion (21.1±0.9 versus 473.8±143.7μg/mg creatinine; P<0.05), but did not affect plasma creatinine. Ang II treatment significantly decreased the medium-chain acyl-CoA dehydrogenase (MCAD), very long-chain acyl-CoA dehydrogenase (VLCAD) (mitochondrial β-oxidation enzymes), cytochrome P-450 (CYP)4A1, and CYP4A2 (microsomal ω-oxidation enzymes) expressions by 20%, 19%, 31% and 17% (P<0.01) in the cortex. It also significantly decreased the MCAD, CYP4A1, CYP4A2 by 38%, 55%, 54% (P<0.01) in the outer medulla, but did not affect the VLCAD expression. In addition, Ang II treatment decreased the peroxisome proliferator-activated receptor (PPAR-α; a nuclear receptor regulating fatty acid oxidation) expression by 30% (P<0.05) in the outer medulla. It did not affect the PPAR-α expression in the cortex and the PPAR-γ coactivator-1α (PGC-1α; a regulator of mitochondrial function) expression both in the cortex and medulla. These data indicate that Ang II down-regulates the MCAD, VLCAD, CYP4A and PPAR-α expressions in the kidney. The suppressed fatty acid oxidation by Ang II may probably cause the renal lipid accumulation, associated with the development of hypertensive kidney damage.