This project will examine the response of the pulmonary endothelial cell of male rats to ionizing radiation. Endothelial cell ultrastructure and function will be determined at various times (1 hr to 6 mo) after a single exposure of 2500 rads of 60 Co gamma rays to the right hemi-thorax. Three indices of endothelial function will be assessed: the activities of both angiotensin converting enzyme (ACE) and plasminogen activator, and the secretion of prostacyclin (PGI2). At each time point, functional changes in the endothelial cell will be correlated with cell ultrastructure. Interactions of the endothelium with formed elements in the blood, and with other cellular components of the lung will be emphasized in the ultrastructural study. Responses of the endothelial cell also will be related to whole organ function as indicated by pulmonary arterial perfusion scans. Changes in the irradiated right lung will be compared with those in the non-irradiated left lung of the same animal. The shielded left lung, in turn, will be compared with lungs of intact, age-matched control rats, in order to observe possible compensatory responses. To determine whether unilateral lung irradiation can produce systemic responses in the hemostatic, fibrinolytic, or renin-angiotensin systems, peripheral blood will be tested for the following: platelets, circulating platelet aggregates, prothrombin and partial thromboplastin times, fibrinogen, fibrin degradation products, aldosterone, corticosterone, and ACE. The ultrastructure of the adrenal cortex and of renal renin granules will also be examined. Finally, we will determine whether the ACE inhibitor, Captopril, or the anti-inflammatory agent, penicillamine, can modify the pathogenesis of radiation injury in the rat lung.
NIH ExPorter
NIH ExPorter