Early effects of ionizing radiation on pulmonary endothelial angiotensin-converting enzyme and 5'-nucleotidase, in vivo.
We investigated the early phase of pulmonary endothelial injury in rabbits exposed to a single dose (30 Gy) of ionizing radiation to the chest, by measuring endothelium-bound ectoenzyme activities. Utilizing multiple indicator-dilution techniques, the metabolism of [3H]benzoyl-Phe-Ala-Pro (BPAP) and [14C]5'-AMP by angiotensin-converting enzyme (ACE) and 5'-nucleotidase (NCT), respectively, was studied during a single transpulmonary passage in conscious, chronically catheterized rabbits. From these data, the apparent kinetic constants Km and Amax were calculated. A significant (p less than 0.05) decrease in the metabolism of trace amounts of BPAP and 5'-AMP was observed at 2, 24, and 48 hr after irradiation. A similar decrease in the apparent first order rate constant (Amax/Km) of ACE was observed at 2 hr, but returned to control levels by 24 and 48 hr after irradiation. Apparent Km values of ACE for BPAP and NCT for 5'-AMP were elevated at 2, 24, and 48 hr post-treatment, whereas Amax (product of enzyme mass and the constant of product formation, kcat) of ACE was elevated at 2 and 24 hr but not at 48 hr, and Amax for NCT was elevated at 2 hr post-treatment only. Significant decreases in mean arterial blood pressure and pulmonary blood flow (Qb) at 2 hr post-treatment, and increases in Qb at 24 and 48 hr post-treatment were also recorded. No changes in endothelial structure were observed 2 hr after irradiation at the light or electron microscope level. We conclude that the early phase of radiation-induced lung injury includes changes in endothelial enzyme function in the absence of structural damage, as reflected in an apparent decrease in affinity of ACE and NCT for their substrates, allowing for the possibility that hemodynamic disturbances or their sequalae could also have contributed to the decrease in enzyme function.
Catravas
J D
JD
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912.
Burch
S E
SE
Spurlock
B O
BO
Mills
L R
LR
D015720:5'-Nucleotidase; D000818:Animals; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D006439:Hemodynamics / Q000528:radiation effects; D007700:Kinetics; D008168:Lung / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D009708:Nucleotidases / Q000528:radiation effects*; D007703:Peptidyl-Dipeptidase A / Q000528:radiation effects*; D011652:Pulmonary Circulation / Q000528:radiation effects; D011817:Rabbits
D009708:Nucleotidases; D015720:5'-Nucleotidase; D007703:Peptidyl-Dipeptidase A