Captopril reduces collagen and mast cell accumulation in irradiated rat lung.
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.
Ward
W F
WF
Dept. of Radiology, Northwestern University Medical School, Chicago, IL 60611.
Molteni
A
A
Ts'ao
C H
CH
Hinz
J M
JM
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002452:Cell Count; D003094:Collagen / Q000378:metabolism*; D006909:Hydroxyproline / Q000032:analysis; D008168:Lung / Q000187:drug effects / Q000528:radiation effects* / Q000648:ultrastructure; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000528:radiation effects*; D009929:Organ Size / Q000187:drug effects / Q000528:radiation effects; D051381:Rats; D011919:Rats, Inbred Strains
D003094:Collagen; D002216:Captopril; D006909:Hydroxyproline