Captopril reduces collagen and mast cell accumulation in irradiated rat lung

Journal Article · Sat Dec 01 00:00:00 EST 1990 · International Journal of Radiation Oncology, Biology and Physics; (USA)

DOI:https://doi.org/10.1016/0360-3016(90)90351-J· OSTI ID:5983930

Ward, W F; Molteni, A; Ts'ao, C H; Hinz, J M ^[1]

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1. Northwestern Univ. Medical School, Chicago, IL (USA)

The angiotensin converting enzyme inhibitor captopril ameliorates radiation-induced pulmonary endothelial dysfunction in rats. The present study determined whether captopril also reduces collagen (hydroxyproline) accumulation in the lungs of rats sacrificed 2 months after a range of single doses (0-30 Gy) of 60Co gamma rays to the right hemithorax. Captopril was administered in the feed at a regimen of 0, 25, or 50 mg/kg/day continuously after irradiation. Mast cell counts also were obtained from lungs of all animals exposed to 30 Gy. In rats receiving no captopril, there was a radiation dose-dependent increase in right lung hydroxyproline (HP) content and in HP concentration per g wet weight. Captopril produced a drug dose-dependent suppression in this radiation-induced HP accumulation. At a dose of 50 mg/kg/d, captopril reduced the slope of the radiation dose response curve for lung HP content by a factor of 1.7, and completely prevented the increase in HP concentration. At an isoeffect level of 550 micrograms HP per right superior lobe, this dose of captopril exhibited a DRF of 1.7 +/- 0.2. In rats exposed to 30 Gy, moreover, the number of mast cells per mm2 of alveolar cross-sectional surface area decreased from 105 +/- 8 to 100 +/- 7 and 59 +/- 5 in the groups given 0, 25 or 50 mg/kg/d of captopril, respectively, (vs none in sham-irradiated rats). These data are the first to demonstrate that the ACE inhibitor captopril might provide a novel intervention in the pathogenesis of radiation fibrosis.

• OSTI ID: 5983930
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (USA), Vol. 19:6; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
COLLAGEN
BIOSYNTHESIS
ENZYME INHIBITORS
RADIOSENSITIVITY EFFECTS
DOSE-RESPONSE RELATIONSHIPS
ENDOTHELIUM
HYDROXYPROLINE
LUNGS
MAST CELLS
RATS
AMINES
AMINO ACIDS
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
AZOLES
BODY
CARBOXYLIC ACIDS
CONNECTIVE TISSUE CELLS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROXY ACIDS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRROLES
PYRROLIDINES
RESPIRATORY SYSTEM
RODENTS
SCLEROPROTEINS
SOMATIC CELLS
SYNTHESIS
TISSUES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals