Document Detail


AT1 receptor antagonist candesartan attenuates genomic damage in peripheral blood lymphocytes of patients on maintenance hemodialysis treatment.
MedLine Citation:
PMID:  21474964     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Angiotensin II (ANG II) and advanced glycation end products (AGEs) exert genotoxic effects in vitro which were prevented by the ANG II type 1 (AT1) receptor blocker, candesartan. In end-stage renal disease (ESRD) the incidence of genomic damage is increased. A stimulation of the renin-angiotensin system and accumulation of AGEs could be involved.
METHODS: We tested whether oral co-administration of candesartan modulates enhanced DNA damage in ESRD patients. Fifteen maintenance hemodialysis (MHD) patients with mild hypertension were treated with candesartan for 4.5 months. Fourteen MHD patients served as conventionally treated uremic controls. DNA damage was measured as micronucleus frequency (MNF) in peripheral blood lymphocytes and evaluated three times before candesartan therapy and afterwards every 6 weeks.
RESULTS: Compared to 14 healthy controls, MNF at baseline was significantly elevated in MHD patients. While in the conventionally treated MHD patients the enhanced DNA damage persisted, the co-administration of candesartan ameliorated the genomic damage significantly and independently of blood pressure changes.
CONCLUSION: Blockade of AT1 receptors with candesartan can reduce DNA damage in MHD patients. Long-term studies in larger patient groups are needed to investigate whether the improved genomic damage lowers atherosclerotic complications and cancer development.
Authors:
Nicole Schupp; Przemyslaw Rutkowski; Katarina Sebeková; André Klassen; Udo Bahner; Clemens Grupp; August Heidland; Helga Stopper
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-07
Journal Detail:
Title:  Kidney & blood pressure research     Volume:  34     ISSN:  1423-0143     ISO Abbreviation:  Kidney Blood Press. Res.     Publication Date:  2011  
Date Detail:
Created Date:  2011-05-20     Completed Date:  2011-09-13     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  9610505     Medline TA:  Kidney Blood Press Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  167-72     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Affiliation:
Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Strasse 9, Würzburg, Germany. nicole.schupp@toxi.uni-wuerzburg.de
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Angiotensin II / antagonists & inhibitors,  toxicity
Angiotensin II Type 1 Receptor Blockers / pharmacology*
Antihypertensive Agents / therapeutic use
Antimutagenic Agents*
Benzimidazoles / pharmacology*
Blood Pressure / physiology
Cell Nucleus / drug effects,  ultrastructure
Cell Separation
Female
Glycosylation End Products, Advanced / antagonists & inhibitors,  toxicity
Humans
Hypertension / drug therapy,  etiology
Kidney Failure, Chronic / blood,  complications,  therapy
Kidney Function Tests
Lymphocytes / drug effects,  physiology*,  ultrastructure*
Male
Micronucleus Tests
Middle Aged
Renal Dialysis / adverse effects*
Tetrazoles / pharmacology*
Chemical
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Antihypertensive Agents; 0/Antimutagenic Agents; 0/Benzimidazoles; 0/Glycosylation End Products, Advanced; 0/Tetrazoles; 11128-99-7/Angiotensin II; S8Q36MD2XX/candesartan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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