PURPOSE: Radiation of the thorax can cause multiple adverse effects to lung tissue. The most frequent adverse effects are pneumonitis and pulmonary fibrosis. This study was designed to evaluate the role of the rennin angiotensin system in lung injury after radiation and the effects of angiotensin converting enzyme (ACE) inhibition in radiation induced lung injury.
METHODS: Adult Wag/Rij received sham or targeted radiation limited to the thorax. Experimental groups were: (1) sham, (2) 12 Grays, (3) 15 Grays, (4) 12 Grays followed by captopril 300 mg/L for 8 weeks. Eight weeks after irradiation, we performed immunohistochemistry (IHC) for angiotensin II in lung tissue and also western blots for angiotensin II receptor type I.
RESULTS: In animals with 12 Grays thoracic radiation, angiotensin II was detected predominantly in alveolar epithelial cells and bronchial wall. There was a 20% increase in staining for angiotensin in rats receiving 12 Grays over control (n=4). This effect was dose dependant because radiation with 15 Gray causes further increase in densitometry (n=4). Animals treated with captopril 300 mg/L after radiation of 12 Grays exhibited attenuated staining for angiotensin II over vehicle treated controls. Western blot for angiotensin II receptor type I showed increased receptor density in rats treated with captopril over those receiving radiation alone. However 12 Gy radiation alone did not cause significant changes in expression of angiotensin II receptor type I over sham.
CONCLUSION: Together these data suggest that the renin angiotensin system is perturbed by radiation lung injury in dose dependant fashion. Chronic treatment with ACE inhibitors decreases expression of angiotensin II in irradiated lungs, and increase expression of angiotensin II receptor type I.
CLINICAL IMPLICATIONS: The renin angiotensin system may have a role in developing radiation induced lung injury. Inhibition of rennin angiotensin system with ACE inhibitors has a potential role in treatment or mitigation of radiation induced lung injury.
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