International journal of radiation oncology, biology, physics, 2009-12, Vol.75 (5), p.1528-1536
2009
Details
- Autor(en) / Beteiligte
- Titel
- Renin-Angiotensin System Suppression Mitigates Experimental Radiation Pneumonitis
- Ist Teil von
- International journal of radiation oncology, biology, physics, 2009-12, Vol.75 (5), p.1528-1536
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- Elsevier ScienceDirect Journals Complete
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0360-3016eISSN: 1879-355XDOI: 10.1016/j.ijrobp.2009.07.1743Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2800372
- Format
- –
- Schlagworte
- ACE, ANGIOTENSIN, Angiotensin Receptor Antagonists, angiotensin-converting enzyme inhibitors, Angiotensin-Converting Enzyme Inhibitors - administration & dosage, Angiotensin-Converting Enzyme Inhibitors - therapeutic use, ANIMALS, BIOLOGICAL EFFECTS, BIOLOGICAL RADIATION EFFECTS, BODY, Captopril - administration & dosage, Captopril - therapeutic use, CARDIOVASCULAR AGENTS, CHEST, DISEASES, Drug Evaluation, Preclinical - methods, DRUGS, ENZYME INHIBITORS, ENZYMES, Female, GLOBULINS, Hematology, Oncology and Palliative Medicine, HYDROLASES, INJURIES, Losartan - administration & dosage, Losartan - therapeutic use, Lung - pathology, Lung - physiopathology, Lung - radiation effects, lung function, MAMMALS, MITIGATION, NONSPECIFIC PEPTIDASES, ORGANIC COMPOUNDS, PEPTIDE HYDROLASES, PNEUMONITIS, PROTEINS, Pulmonary Artery - drug effects, Pulmonary Artery - physiology, Pulmonary Artery - radiation effects, Radiation Dosage, RADIATION EFFECTS, RADIATION INJURIES, Radiation Injuries, Experimental - drug therapy, Radiation Injuries, Experimental - mortality, Radiation Injuries, Experimental - pathology, Radiation Injuries, Experimental - physiopathology, Radiation injury, Radiation Pneumonitis - drug therapy, Radiation Pneumonitis - mortality, Radiation Pneumonitis - pathology, Radiation Pneumonitis - physiopathology, RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS, Radiology, RATS, RENIN, Renin-Angiotensin System - drug effects, Renin-Angiotensin System - physiology, Respiratory Mechanics - drug effects, Respiratory Mechanics - physiology, Respiratory Mechanics - radiation effects, RODENTS, Time Factors, Vasoconstriction - drug effects, Vasoconstriction - physiology, Vasoconstriction - radiation effects, VASOCONSTRICTORS, Vasodilation - drug effects, Vasodilation - physiology, Vasodilation - radiation effects, VERTEBRATES