title: AT1 receptor antagonist candesartan attenuates genomic damage in peripheral blood lymphocytes of patients on maintenance hemodialysis treatment.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Strasse 9, Würzburg, Germany. nicole.schupp@toxi.uni-wuerzburg.de
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupp
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Rutkowski
authors.forename: Katarina
authors.initials: K
authors.lastname: Sebeková
authors.forename: André
authors.initials: A
authors.lastname: Klassen
authors.forename: Udo
authors.initials: U
authors.lastname: Bahner
authors.forename: Clemens
authors.initials: C
authors.lastname: Grupp
authors.forename: August
authors.initials: A
authors.lastname: Heidland
authors.forename: Helga
authors.initials: H
authors.lastname: Stopper
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000633:toxicity; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D016587:Antimutagenic Agents; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000502:physiology; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002469:Cell Separation; D005260:Female; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000633:toxicity; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D007677:Kidney Function Tests; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D016587:Antimutagenic Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D017127:Glycation End Products, Advanced; D013777:Tetrazoles; D000804:Angiotensin II; C081643:candesartan