Functional responses of the pulmonary endothelium to thoracic irradiation in rats: Differential modification by D-penicillamine
| Autor: | C. Ts'ao, Norman H. Solliday, Agostino Molteni, William F. Ward |
|---|---|
| Rok vydání: | 1987 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Pathology Endothelium Thromboxane Radiation-Protective Agents Prostacyclin Peptidyl-Dipeptidase A Plasminogen Activators Internal medicine medicine Animals Radiology Nuclear Medicine and imaging Endothelial dysfunction Lung Radiation medicine.diagnostic_test biology business.industry Penicillamine Thromboxanes Angiotensin-converting enzyme medicine.disease Epoprostenol Rats Bronchoalveolar lavage Endocrinology medicine.anatomical_structure Oncology Eicosanoid biology.protein lipids (amino acids peptides and proteins) business circulatory and respiratory physiology medicine.drug |
| Zdroj: | International Journal of Radiation Oncology*Biology*Physics. 13:1505-1513 |
| ISSN: | 0360-3016 |
| DOI: | 10.1016/0360-3016(87)90318-x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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