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Renin-Angiotensin system suppression mitigates experimental radiation pneumonitis.

AbstractPURPOSE:
To find the mitigators of pneumonitis induced by moderate doses of thoracic radiation (10-15 Gy).
METHODS AND MATERIALS:
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.
CONCLUSION:
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.
AuthorsSwarajit N Ghosh, Rong Zhang, Brian L Fish, Vladimir A Semenenko, X Allen Li, John E Moulder, Elizabeth R Jacobs, Meetha Medhora
JournalInternational journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 75 Issue 5 Pg. 1528-36 (Dec 1 2009) ISSN: 1879-355X [Electronic] United States
PMID19931735 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Captopril
  • Losartan
Topics
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors (administration & dosage, therapeutic use)
  • Animals
  • Captopril (administration & dosage, therapeutic use)
  • Drug Evaluation, Preclinical (methods)
  • Female
  • Losartan (administration & dosage, therapeutic use)
  • Lung (pathology, physiopathology, radiation effects)
  • Pulmonary Artery (drug effects, physiology, radiation effects)
  • Radiation Dosage
  • Radiation Injuries, Experimental (drug therapy, mortality, pathology, physiopathology)
  • Radiation Pneumonitis (drug therapy, mortality, pathology, physiopathology)
  • Rats
  • Renin-Angiotensin System (drug effects, physiology)
  • Respiratory Mechanics (drug effects, physiology, radiation effects)
  • Time Factors
  • Vasoconstriction (drug effects, physiology, radiation effects)
  • Vasodilation (drug effects, physiology, radiation effects)

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