Bilirubin exerts renoprotective effects in angiotensin II-hypertension.
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 that 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 and resultant proteinuria, 2 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 in 1 group (3 mg/100 g body weight/48 hr, intraperitoneally). Two weeks after onset of Ang II infusion, systolic blood pressure significantly increased from 134 +/- 4 to 198 +/- 7 mm Hg (P < 0.05) in the Ang II group and from 128 +/- 8 to 209 +/- 9 mm Hg (P < 0.05) in the Ang II + bilirubin group. Relative to the Ang II group, treatment with bilirubin did not alter body weight, food intake, water intake or urine output. However, urinary protein excretion was significantly lower in the Ang II + bilirubin group (32.9 +/- 9.7 mg/d versus 81.4 +/- 22.8 mg/d, P < 0.05). The authors conclude that exogenous bilirubin exerts renoprotective effects in Ang II-dependent hypertension.
LeBlanc
Ryan M
RM
Department of Physiology, Hypertension and Renal Center, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Navar
L Gabriel
LG
Botros
Fady T
FT
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D011507:Proteinuria / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000804:Angiotensin II; D001663:Bilirubin