Radiation-induced endothelial dysfunction and fibrosis in rat lung: modification by the angiotensin converting enzyme inhibitor CL242817

Journal Article · Wed Feb 01 04:00:00 EST 1989 · Radiat. Res.; (United States)

DOI:https://doi.org/10.2307/3577335· OSTI ID:6072413

Ward, W F; Molteni, A; Ts'ao, C H

The purpose of this study was to evaluate the angiotensin converting enzyme (ACE) inhibitor CL242817 as a modifier of radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a single dose of 60Co gamma rays (0-30 Gy) to the right hemithorax. CL242817 was administered in the feed continuously after irradiation at a regimen of 60 mg/kg/day. Pulmonary endothelial function was monitored by lung ACE activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Pulmonary fibrosis was evaluated by lung hydroxyproline (HP) content. Lung ACE and PLA activities decreased with increasing radiation dose, and cotreatment with CL242817 significantly ameliorated both responses. CL242817 dose-reduction factors (DRF) were 1.3-1.5 for ACE and PLA activity. Lung PGI2 and TXA2 production increased with increasing radiation dose, and CL242817 almost completely prevented both radiation responses. The slope of the radiation dose-response curves in the CL242817-treated rats was essentially zero, precluding calculation of DRF values for PGI2 and TXA2 production. Lung HP content also increased with increasing radiation dose, and CL242817 significantly attenuated this response (DRF = 1.5). These data suggest that the ability of ACE inhibitors to ameliorate radiation-induced pulmonary endothelial dysfunction is not unique to captopril, rather it is a therapeutic action shared by other members of this class of compounds. These data also provide the first evidence that ACE inhibitors exhibit antifibrotic activity in irradiated rat lung.

• Research Organization: Northwestern Univ. Medical School, Chicago, IL (USA)
• OSTI ID: 6072413
• Journal Information: Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 117:2; ISSN RAREA
• 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.
AMINES
AMINO ACIDS
ANIMAL TISSUES
ANIMALS
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
COBALT 60
COBALT ISOTOPES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
ELECTROMAGNETIC RADIATION
ENDOTHELIUM
ENZYME INHIBITORS
ENZYMES
FIBROSIS
GAMMA RADIATION
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROLASES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IONIZING RADIATIONS
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LUNGS
MAMMALS
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PEPTIDE HYDROLASES
PROLINE
PROSTAGLANDINS
PYRROLES
PYRROLIDINES
RADIATIONS
RADIOINDUCTION
RADIOISOTOPES
RADIOSENSITIVITY EFFECTS
RATS
RESPIRATORY SYSTEM
RESPIRATORY SYSTEM DISEASES
RODENTS
TISSUES
VERTEBRATES
YEARS LIVING RADIOISOTOPES