Renin-Angiotensin system suppression mitigates experimental radiation pneumonitis. Int J Radiat Oncol Biol Phys 2009 Dec 01;75(5):1528-36
Date
11/26/2009Pubmed ID
19931735Pubmed Central ID
PMC2800372DOI
10.1016/j.ijrobp.2009.07.1743Scopus ID
2-s2.0-71649101555 (requires institutional sign-in at Scopus site) 102 CitationsAbstract
PURPOSE: 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.
Author List
Ghosh SN, Zhang R, Fish BL, Semenenko VA, Li XA, Moulder JE, Jacobs ER, Medhora MAuthors
Elizabeth R. Jacobs MD Emeritus Professor in the Medicine department at Medical College of WisconsinMeetha Medhora Professor in the Radiation Oncology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Angiotensin Receptor AntagonistsAngiotensin-Converting Enzyme Inhibitors
Animals
Captopril
Drug Evaluation, Preclinical
Female
Losartan
Lung
Pulmonary Artery
Radiation Dosage
Radiation Injuries, Experimental
Radiation Pneumonitis
Rats
Renin-Angiotensin System
Respiratory Mechanics
Time Factors
Vasoconstriction
Vasodilation
