Mitigation of radiation induced pulmonary vascular injury by delayed treatment with captopril. Respirology 2012 Nov;17(8):1261-8
Date
08/14/2012Pubmed ID
22882664Pubmed Central ID
PMC3848310DOI
10.1111/j.1440-1843.2012.02247.xScopus ID
2-s2.0-84867930386 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
BACKGROUND AND OBJECTIVE: A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin-converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2 months post-exposure. In this study, we evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage.
METHODS: Rats exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2 months after exposure, during the development of radiation pneumonitis. Rats were treated, either immediately or 2 weeks after radiation exposure, with two doses of the ACE inhibitor, captopril, dissolved in their drinking water. To determine pulmonary vascular responses, we measured pulmonary haemodynamics, lung ACE activity, pulmonary arterial distensibility and peripheral vessel density.
RESULTS: Captopril, given at a vasoactive, but not a lower dose, mitigated radiation-induced pulmonary vascular injury. More importantly, these beneficial effects were observed even if drug therapy was delayed for up to 2 weeks after exposure.
CONCLUSIONS: Captopril resulted in a reduction in pulmonary vascular injury that supports its use as a radiomitigator after an unexpected radiological event such as a nuclear accident.
Author List
Molthen RC, Wu Q, Fish BL, Moulder JE, Jacobs ER, Medhora MMMESH terms used to index this publication - Major topics in bold
Acute Lung InjuryAngiotensin-Converting Enzyme Inhibitors
Animals
Captopril
Female
Lung
Radiation Dosage
Radiation Injuries
Radiation Pneumonitis
Rats
Thorax
Vascular System Injuries