LOCALIZATION OF [I-125] ENDOTHELIN-1 IN INJURED AORTA OF RABBITS

Endothelin-1 is a potent vasoconstrictor. This study was performed to determine whether arterial injury, induced by either hypercholesterolemia or mechanical disruption of the endothelium, is associated with increased localization of endothelin-1 in the artery. The blood clearance and tissue distribution of intravenously injected [I-125]endothelin-1 was evaluated in 33 rabbits control animals (n = 7), balloon de-endothelialized animals (n = 12), cholesterol-fed animals (n = 6) and animals that had both balloon de-endothelialization and high cholesterol diet (n = 8). The blood clearance half time was less than 10 min, with slightly slower clearance in the ballooned/cholesterol-fed animals. [I-125]Endothelin-1 localized in the lung (similar to 12% injected dose (ID)/organ) and kidney(similar to 8%ID/organ). [I-125]Endothelin-1 localization in the injured aorta increased from the baseline level of 0.06%kgID/g to its highest level within 5 min of balloon de-endothelialization (0.2%kgID/g) and decreased to 0.11%kgID/g within one week and remained essentially unchanged through 16 weeks. The area with increased binding of [I-125]endothelin-1 corresponded to the zone of arterial injury stained with Evans blue. On the other hand, the binding in the aorta did not increase with the atherogenic diet. These findings suggest that endothelin-1 accumulates in injured vessels, attaining the highest levels immediately after mechanical injury.