Functional responses of the pulmonary endothelium to thoracic irradiation in rats: differential modification by D-penicillamine

Journal Article · Thu Oct 01 04:00:00 EDT 1987 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(87)90318-X· OSTI ID:6018856

Ward, W F; Molteni, A; Ts'ao, C; Solliday, N H

Male rats were sacrificed 2 or 6 months after a range of single doses of gamma rays (0-30 Gy) to the right hemithorax. Half of each dose group consumed control feed continuously after irradiation, and half consumed feed containing the collagen antagonist D-penicillamine (10 mg/rat/day). Four markers of pulmonary endothelial function were monitored: angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Bronchoalveolar lavage (BAL) fluid also was obtained from the right lung, and was analyzed for macrophage number, and PGI2 and TXA2 concentration. Right lung ACE and PLA activities decreased linearly with increasing dose at both 2 and 6 months postirradiation, and penicillamine had no significant effect on either response. In contrast, PGI2 and TXA2 production by the right lung increased linearly with increasing radiation dose at both autopsy times. Penicillamine significantly ameliorated the increase in PGI2 production at 2 months, and the increase in TXA2 production at both 2 and 6 months postirradiation. Penicillamine dose-reduction factors (DRF) for PGI2 and TXA2 production were 1.3-1.4, and the response curve slope ratios were 1.7-2.5 (p less than 0.05). Penicillamine also ameliorated the dose-dependent increase in TXA2 concentration in the BAL fluid at 2 months. These data indicate that the four markers of radiation-induced pulmonary endothelial dysfunction do not respond identically to penicillamine dose-modification. Of the four markers, TXA2 production exhibits the most significant and widespread penicillamine sparing. TXA2 is a potent vasoconstrictor, promoter of platelet aggregation, and mediator of inflammation, and partial prevention of the radiation-induced hyperproduction of this eicosanoid may account in part for penicillamine's therapeutic action in this model.

• Research Organization: Northwestern Univ. Medical School, Chicago, IL
• OSTI ID: 6018856
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 13:10; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACUTE EXPOSURE
ACUTE IRRADIATION
AMINO ACIDS
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL MARKERS
BODY
BODY AREAS
CARBOXYLIC ACIDS
CHELATING AGENTS
CHEST
CONNECTIVE TISSUE CELLS
DOSE-RESPONSE RELATIONSHIPS
DOSES
DRUGS
DYNAMIC FUNCTION STUDIES
ELECTROMAGNETIC RADIATION
ENDOTHELIUM
ENZYME ACTIVITY
GAMMA RADIATION
IONIZING RADIATIONS
IRRADIATION
LAVAGE
LUNGS
MACROPHAGES
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PENICILLAMINE
PHAGOCYTES
PROSTAGLANDINS
RADIATION DOSES
RADIATIONS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RATS
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
THIOLS
TISSUES
VERTEBRATES