Radiation-induced pulmonary endothelial dysfunction in rats: modification by an inhibitor of angiotensin converting enzyme

Journal Article · Fri Jul 01 04:00:00 EDT 1988 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(88)90357-4· OSTI ID:7184505

Ward, W F; Kim, Y T; Molteni, A; Solliday, N H

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 /sup 60/Co 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.

• Research Organization: Northwestern Univ. Medical School, Chicago, IL (USA)
• OSTI ID: 7184505
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 15:1; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
COBALT 60
COBALT ISOTOPES
DOSE-RESPONSE RELATIONSHIPS
ELECTROMAGNETIC RADIATION
ENDOTHELIUM
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
GAMMA RADIATION
HYDROLASES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IONIZING RADIATIONS
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
MATHEMATICS
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-ODD NUCLEI
PEPTIDE HYDROLASES
PROSTAGLANDINS
RADIATION EFFECTS
RADIATIONS
RADIOISOTOPES
RADIOSENSITIVITY EFFECTS
RATS
REGRESSION ANALYSIS
RODENTS
STATISTICS
TISSUES
VERTEBRATES
YEARS LIVING RADIOISOTOPES