Captopril reduces collagen and mast cell accumulation in irradiated rat lung.

Abstract

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.

• Authors: W F Ward, A Molteni, C H Ts'ao, J M Hinz
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 19 Issue 6 Pg. 1405-9 (Dec 1990) ISSN: 0360-3016 [Print] United States
• PMID: 2262365 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Collagen
• Captopril
• Hydroxyproline

Topics

• Animals
• Captopril (pharmacology)
• Cell Count
• Collagen (metabolism)
• Hydroxyproline (analysis)
• Lung (drug effects, radiation effects, ultrastructure)
• Male
• Mast Cells (drug effects, radiation effects)
• Organ Size (drug effects, radiation effects)
• Rats
• Rats, Inbred Strains