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Moderate Hyperbilirubinemia Improves Renal Hemodynamics in Angiotensin II‐Dependent Hypertension
Author(s) -
Stec David E.,
Vera Trinity
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1025.11
Subject(s) - endocrinology , angiotensin ii , renal function , medicine , indinavir , renal blood flow , valsartan , nitric oxide , chemistry , kidney , blood pressure , immunology , virus , sida , viral disease
We have previously demonstrated that moderate hyperbilirubinemia decreases blood pressure in Angiotensin (Ang) II‐dependent hypertension through mechanisms that decrease oxidative stress and increase nitric oxide levels. The goal of the present study was to examine the effect of moderate hyperbilirubinemia on glomerular filtration rate (GFR) and renal blood flow (RBF) in a mouse model of Ang II hypertension. Mice were made moderately hyperbilirubinemic by treatment with 1) indinavir or 2) morpholino antisense oligonucleotides directed against hepatic UGT1A1. Levels of unconjugated bilirubin averaged 0.57 ± 0.07, 0.92 ± 0.07, and 1.28 ± 0.1 mg/dL (n=4) in control, indinavir, and antisense treated mice, respectively. GFR and RBF were measured in mice after implantation of an osmotic minipump delivering Ang II at a rate of 1 μg/kg/min. GFR was measured by continuous infusion of I 125 ‐iothalamate on days 7–11 of Ang II infusion in conscious mice. RBF was measured on day 10 of Ang II infusion in anesthetized mice. Treatment with either indinavir or UGT1A1 antisense significantly increased GFR in Ang II infused mice 1.2 ± 0.1, 1.9 ± 0.2, and 1.9 ± 0.1 ml/min/g kidney weight (n=4) in non‐treated, indinavir, and antisense treated mice, respectively. Next, we examined the effect of moderate hyperbilirubinemia on RBF in Ang II infused mice. Ang II infusion significantly decreased RBF and this decrease was normalized by moderate hyperbilirubinemia with RBF averaging 5.2 ± 0.5, 3.8 ± 0.2, and 4.8 ± 0.3 ml/min/g kw (n=4) in control, Ang II, and Ang II+indinavir treated mice, respectively. These results indicate that improvement of renal hemodynamics may be a mechanism by which blood pressure is lowered with moderate hyperbilirubinemia in this model. This study was supported by NIH grant HL‐088421.