Pulmonary endothelial dysfunction induced by unilateral as compared to bilateral thoracic irradiation in rats.
Rats were sacrificed 2 months after a single dose of 10-30 Gy of 60Co gamma rays delivered to either a right unilateral or a bilateral thoracic port. Four indices of lung endothelial function were measured: the activities of angiotensin-converting enzyme (ACE) and plasminogen activator (PLA) and the production of prostacyclin (PGI2) and thromboxane (TXA2). The number of macrophages recovered by bronchoalveolar lavage (BAL) and the degree of right ventricular hypertrophy (an index of pulmonary hypertension) also were determined. Right lung ACE and PLA activity decreased linearly, and PGI2 and TXA2 production increased linearly with increasing radiation dose. The response curves for right unilateral and bilateral thoracic irradiation were not significantly different. In contrast, bilateral irradiation was more toxic than unilateral, since rats exposed to the former exhibited decreased body weight, an increased incidence of pleural effusions, an increase in the number of macrophages recovered by BAL, and right ventricular hypertrophy. These data demonstrate that pulmonary endothelial dysfunction induced by hemithorax irradiation represents a direct response of the endothelium to radiation injury and is not secondary to other phenomena such as shunting of function to the shielded lung.
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004727:Endothelium / Q000528:radiation effects; D011464:Epoprostenol / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013931:Thromboxanes / Q000378:metabolism
D013931:Thromboxanes; D011464:Epoprostenol; D007703:Peptidyl-Dipeptidase A; D010960:Plasminogen Activators