Exogenous bilirubin administration exerts renoprotective effects in angiotensin II‐hypertension

Abstract

Bilirubin is an endogenous antioxidant and is the end product of heme catabolism by heme oxygenase (HO) and biliverdin reductase. Chronic angiotensin II (Ang II) infusion induces renal HO‐1 expression which is associated with renoprotective effects, and further induction of renal HO‐1 attenuates the development of hypertension in this model. To determine the effects of bilirubin on the development of Ang II‐induced hypertension, two groups of rats were studied: Ang II (n=4) and Ang II+Bilirubin (n=4). Rats were infused with Ang II (80 ng/min for 2 weeks) and bilirubin was administered simultaneously (3mg/100g BWt/48 hrs, intraperitoneally). Two weeks after Ang II infusion, systolic blood pressure significantly increased from 134±4 mmHg to 198±7 mmHg (p<0.05) in the Ang II group, and from 128±8 mmHg to 209±9 mmHg (p<0.05) in the Ang II+Bilirubin group. Relative to the Ang II group, treatment with bilirubin did not alter body weight 259±18 g vs. 275±18 g, food intake 25±3 g vs. 25±2 g, water intake 78.1±6.7 vs. 75.3±7.3 ml/day, or urine output 58.5±5.8 ml vs. 50.8±5.5 ml/day. However, urinary protein excretion was significantly lower in the Ang II+Bilirubin group (32.9±9.7 mg/day vs. 81.4±22.8 mg/day, p<0.05). We conclude that bilirubin contributes to the renoprotective effects conferred by induction of HO‐1 in Ang II‐dependent hypertension. Supported by NIH grants HL26371 and COBRE P20 RR 017659.