Mitigation of radiation induced pulmonary vascular injury by delayed treatment with captopril.

Abstract

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.

• Authors: Robert C Molthen, Qingping Wu, Brian L Fish, John E Moulder, Elizabeth R Jacobs, Meetha M Medhora
• Journal: Respirology (Carlton, Vic.) (Respirology) Vol. 17 Issue 8 Pg. 1261-8 (Nov 2012) ISSN: 1440-1843 [Electronic] Australia
• PMID: 22882664 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Captopril

Topics

• Acute Lung Injury (drug therapy)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Animals
• Captopril (therapeutic use)
• Female
• Lung (blood supply, drug effects, enzymology, radiation effects)
• Radiation Dosage
• Radiation Injuries (drug therapy, enzymology)
• Radiation Pneumonitis (drug therapy, enzymology)
• Rats
• Thorax (drug effects, radiation effects)
• Vascular System Injuries (drug therapy)