Abstract |
Our long-term goal is to use angiotensin converting enzyme ( ACE) inhibitors to mitigate the increase in lung collagen synthesis that is induced by irradiation to the lung, which could result from accidental exposure or radiological terrorism. Rats (WAG/RijCmcr) were given a single dose of 13 Gy (dose rate of 1.43 Gy/min) of X-irradiation to the thorax. Three structurally-different ACE inhibitors, captopril, enalapril and fosinopril were provided in drinking water beginning 1 week after irradiation. Rats that survived acute pneumonitis (at 6-12 weeks) were evaluated monthly for synthesis of lung collagen. Other endpoints included breathing rate, wet to dry lung weight ratio, and analysis of lung structure. Treatment with captopril (145-207 mg/m(2)/day) or enalapril (19-28 mg/m(2)/day), but not fosinopril (19-28 mg/m(2)/day), decreased morbidity from acute pneumonitis. Lung collagen in the surviving irradiated rats was increased over that of controls by 7 months after irradiation. This increase in collagen synthesis was not observed in rats treated with any of the three ACE inhibitors. Analysis of the lung morphology at 7 months supports the efficacy of ACE inhibitors against radiation-induced fibrosis. The effectiveness of fosinopril against fibrosis, but not against acute pneumonitis, suggests that pulmonary fibrosis may not be a simple consequence of injury during acute pneumonitis. In summary, three structurally-different ACE inhibitors mitigate the increase in collagen synthesis 7 months following irradiation of the whole thorax and do so, even when therapy is started one week after irradiation.
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Authors | Lakhan Kma, Feng Gao, Brian L Fish, John E Moulder, Elizabeth R Jacobs, Meetha Medhora |
Journal | Journal of radiation research
(J Radiat Res)
Vol. 53
Issue 1
Pg. 10-7
( 2012)
ISSN: 1349-9157 [Electronic] England |
PMID | 22302041
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Angiotensin-Converting Enzyme Inhibitors
- Enalapril
- Collagen
- Captopril
- Fosinopril
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Topics |
- Angiotensin-Converting Enzyme Inhibitors
(pharmacology, therapeutic use)
- Animals
- Captopril
(pharmacology, therapeutic use)
- Collagen
(biosynthesis)
- Dose-Response Relationship, Radiation
- Drug Evaluation, Preclinical
- Enalapril
(pharmacology, therapeutic use)
- Female
- Fibrosis
- Fosinopril
(pharmacology, therapeutic use)
- Gene Expression Regulation
(radiation effects)
- Lung
(drug effects, metabolism, pathology, radiation effects)
- Pulmonary Fibrosis
(etiology, metabolism, pathology, prevention & control)
- Radiation Pneumonitis
(complications, drug therapy, metabolism, pathology)
- Rats
- Renin-Angiotensin System
(physiology)
- Thorax
(radiation effects)
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