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.