Radiation-induced pulmonary endothelial dysfunction in rats: modification by an inhibitor of angiotensin converting enzyme.
The ability of the angiotensin converting enzyme (ACE) inhibitor Captopril to modify radiation-induced pulmonary endothelial dysfunction was determined in male rats sacrificed 2 months after a single dose of 10-30 Gy of 60Co gamma rays to the right hemithorax. Half of each dose group consumed feed containing 0.12% w/w Captopril (60 mg/kg/day) continuously after irradiation, and half consumed control feed. Four markers of endothelial function were monitored: ACE activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. All data were plotted as dose-response curves, and subjected to linear regression analysis. The Captopril modifying effect was expressed as the ratio of isoeffective doses at a common intermediate response (DRF), or as the ratio of the response curve slopes. Right lung ACE and PLA activity decreased linearly, and PGI2 and TXA2 production increased linearly with increasing radiation dose. Captopril exhibited DRF values of 1.4-2.1, and slope ratios of 1.4-5.1 for all four functional markers (p less than 0.05). Thus, the ACE inhibitor Captopril ameliorates radiation-induced pulmonary endothelial dysfunction in rats sacrificed 2 months postirradiation. Although the mechanism of Captopril action is not clear at present, these data suggest a novel application for this class of compounds as injury-modifying agents in irradiated lung.
Ward
W F
WF
Department of Radiology, Northwestern University Medical School, Chicago, IL 60611.
Kim
Y T
YT
Molteni
A
A
Solliday
N H
NH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D004727:Endothelium / Q000187:drug effects / Q000528:radiation effects; D008168:Lung / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril