Early effects of ionizing radiation on pulmonary endothelial angiotensin-converting enzyme and 5'-nucleotidase, in vivo

Journal Article · Fri Jul 01 04:00:00 EDT 1988 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(88)90276-1· OSTI ID:6922986

Catravas, J D; Burch, S E; Spurlock, B O; Mills, L R

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 (/sup 3/H)benzoyl-Phe-Ala-Pro (BPAP) and (/sup 14/C)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 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 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.

• Research Organization: Medical College of Georgia, Augusta (USA)
• OSTI ID: 6922986
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 94:3; ISSN TXAPA
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560152* -- Radiation Effects on Animals-- Animals
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACUTE EXPOSURE
ACUTE IRRADIATION
ANIMAL TISSUES
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BLOOD CIRCULATION
BLOOD PRESSURE
BODY
BODY AREAS
CARBON 14 COMPOUNDS
CHEST
ENDOTHELIUM
ENZYME ACTIVITY
ENZYMES
ESTERASES
HYDROLASES
IN VIVO
IONIZING RADIATIONS
IRRADIATION
LABELLED COMPOUNDS
LUNGS
MAMMALS
METABOLISM
NUCLEOTIDASES
ORGANS
PEPTIDE HYDROLASES
PHOSPHATASES
RABBITS
RADIATION EFFECTS
RADIATIONS
RESPIRATORY SYSTEM
TISSUES
TRITIUM COMPOUNDS
VERTEBRATES