Radiation injury in rat lung. II. Angiotensin-converting enzyme activity.
To determine the role of endothelial dysfunction in the pathogenesis of radiation-induced pulmonary injury, lung angiotensin-converting enzyme (ACE) activity, arterial perfusion, and ultrastructure were examined from 1 to 150 days after a single exposure of 25 Gy of 60Co gamma rays to the right hemithorax of rats. Arterial perfusion to the irradiated right lung increased during the first 2 weeks, then decreased to approximately 80% of the left lung value at 30 days postirradiation. Perfusion of the irradiated lung continued to decline, and by 90-150 days was only 40% of that of the shielded lung. ACE activity in the irradiated right lung did not change significantly until 30 days after exposure, when it decreased to 72% of that in the left lung. ACE activity in the right lung declined steadily from 30 to 90 days postirradiation, then reached a plateau through 150 days at less than 20% of normal. Perivascular and interstitial edema was evident at 1 day after irradiation and persisted for 30 days. Endothelial cells exhibited blebbing, fragmentation, and increased basement membrane at 30 days. Mast cells were present in the septa, but interstitial collagen was not increased at that time. From 90 to 150 days postexposure, progressive obliteration of capillaries by fibrotic reactions was observed. Thus decreased ACE activity accompanies radiation-induced hypoperfusion and endothelial ultrastructural changes in rat lung. All of these reactions precede the development of pulmonary fibrosis.
D000818:Animals; D004727:Endothelium / Q000201:enzymology / Q000528:radiation effects; D005720:Gamma Rays; D006976:Hypertension, Pulmonary / Q000209:etiology; D008168:Lung / Q000201:enzymology / Q000528:radiation effects* / Q000648:ultrastructure; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000528:radiation effects*; D011651:Pulmonary Artery / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000201:enzymology* / Q000209:etiology; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000528:radiation effects; D013997:Time Factors
D007703:Peptidyl-Dipeptidase A