Document Detail


Moderate hyperbilirubinemia improves renal hemodynamics in ANG II-dependent hypertension.
MedLine Citation:
PMID:  20668235     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously demonstrated that moderate hyperbilirubinemia decreases blood pressure in ANG II-dependent hypertension through mechanisms that decrease oxidative stress and increase nitric oxide levels. Since decreases in renal hemodynamics play an important role in mediating the hypertensive actions of ANG II, 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 two methods: indinavir or specific morpholino antisense oligonucleotides against UGT1A1, which is the enzyme responsible for the conjugation of bilirubin in the liver. GFR and RBF were measured in mice after implantation of an osmotic minipump delivering ANG II at a rate of 1 μg·kg(-1)·min(-1). GFR was measured by continuous infusion of I(125)-labeled iothalamate on days 5 and 6 of ANG II infusion in conscious mice. RBF was measured on day 7 of ANG II infusion in anesthetized mice. Blood levels of unconjugated bilirubin were significantly increased in mice treated with indinavir or anti-UGT1A1 (P = 0.002). ANG II decreased GFR by 33% of control (n = 9, P = 0.004), and this was normalized by moderate hyperbilirubinemia (n = 6). Next, we examined the effect of moderate hyperbilirubinemia on RBF in ANG II-infused mice. ANG II infusion significantly decreased RBF by 22% (P = 0.037) of control, and this decrease was normalized by moderate hyperbilirubinemia (n = 6). These results indicate that improvement of renal hemodynamics may be one mechanism by which moderate hyperbilirubinemia lowers blood pressure in this model.
Authors:
Trinity Vera; David E Stec
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-07-28
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  299     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-01     Completed Date:  2010-10-19     Revised Date:  2014-03-28    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1044-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / physiology*
Animals
Bilirubin / blood
Blotting, Western
Glomerular Filtration Rate / physiology
Glucuronosyltransferase / metabolism
Hyperbilirubinemia / physiopathology*
Hypertension / physiopathology*
Indinavir / pharmacology
Liver / drug effects,  metabolism
Male
Mice
Mice, Inbred C57BL
Morpholines / pharmacology
Oligonucleotides, Antisense / pharmacology
Organic Cation Transport Proteins / metabolism
Protein Synthesis Inhibitors / pharmacology
Renal Circulation / physiology*
Grant Support
ID/Acronym/Agency:
HL088421/HL/NHLBI NIH HHS; P01HL51971/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Morpholines; 0/Oatp2 protein, mouse; 0/Oligonucleotides, Antisense; 0/Organic Cation Transport Proteins; 0/Protein Synthesis Inhibitors; 11128-99-7/Angiotensin II; 5W6YA9PKKH/Indinavir; EC 2.4.1.17/Glucuronosyltransferase; RFM9X3LJ49/Bilirubin
Comments/Corrections

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