title: Renin-Angiotensin system suppression mitigates experimental radiation pneumonitis.
abstract: OBJECTIVE
  To find the mitigators of pneumonitis induced by moderate doses of thoracic radiation (10-15 Gy).
  
  
  METHODS
  Unanesthetized WAG/RijCmcr female rats received a single dose of X-irradiation (10, 12, or 15 Gy at 1.615 Gy/min) to the thorax. Captopril (an angiotensin-converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in the drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating the breathing rate, ex vivo vascular reactivity, and histopathologic findings. Survival analysis was undertaken on all animals, except those scheduled for death.
  
  
  RESULTS
  Survival after a dose of 10 Gy to the thorax was not different from that of unirradiated rats for <or=1 year. Survival decreased to <50% by 45 weeks after 12 Gy and by 8-9 weeks after 15 Gy. Captopril (17-56 mg/kg/d) improved survival and reduced radiation-induced increases in breathing rate, changes in vascular reactivity, and histopathologic evidence of injury. Radiation-induced increases in the breathing rate were prevented even if captopril was started 1 week after irradiation or if it was discontinued after 5 weeks. Losartan, although effective in reducing mortality, was not as efficacious as captopril in mitigating radiation-induced increases in the breathing rate or altered vasoreactivity.
  
  
  CONCLUSIONS
  In rats, a moderate thoracic radiation dose induced pneumonitis and morbidity. These injuries were mitigated by captopril even when it was begun 1 week after radiation or if discontinued 5 weeks after exposure. Losartan was less effective in protecting against radiation-induced changes in vascular reactivity or tachypnea.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care, Medical College of Wisconsin, Milwaukee, WI 53226, USA. snghosh@mcw.edu
authors.forename: Swarajit N
authors.initials: SN
authors.lastname: Ghosh
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Brian L
authors.initials: BL
authors.lastname: Fish
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Semenenko
authors.forename: X Allen
authors.initials: XA
authors.lastname: Li
authors.forename: John E
authors.initials: JE
authors.lastname: Moulder
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Jacobs
authors.forename: Meetha
authors.initials: M
authors.lastname: Medhora
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D008168:Lung / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D017564:Radiation Pneumonitis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D019808:Losartan