Renin-Angiotensin System Suppression Mitigates Experimental Radiation Pneumonitis

Journal Article · Tue Dec 01 00:00:00 EST 2009 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.07.1743· OSTI ID:21367566

Rong, Zhang ^[1]; Fish, Brian L; Semenenko, Vladimir A; Li, X Allen; Moulder, John E ^[2]; Jacobs, Elizabeth R; Medhora, Meetha ^[1]

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1. Department of Medicine, Division of Pulmonary and Critical Care, Medical College of Wisconsin, Milwaukee, WI (United States)
2. Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

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 <=1 year. Survival decreased to <50% by 45 weeks after 12 Gy and by 8-9 weeks after 15 Gy. Captopril (17-56mg/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.

• OSTI ID: 21367566
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 75, Issue 5; Other Information: DOI: 10.1016/j.ijrobp.2009.07.1743; PII: S0360-3016(09)02929-0; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
ANGIOTENSIN
CHEST
ENZYME INHIBITORS
MITIGATION
PNEUMONITIS
RADIATION INJURIES
RATS
RENIN
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
CARDIOVASCULAR AGENTS
DISEASES
DRUGS
ENZYMES
GLOBULINS
HYDROLASES
INJURIES
MAMMALS
NONSPECIFIC PEPTIDASES
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PROTEINS
RADIATION EFFECTS
RODENTS
VASOCONSTRICTORS
VERTEBRATES