Vascular responses to endothelin-1 in atherosclerotic primates

Endothelin-1 (ET-1) is a vasoactive peptide that is released by endothelial cells. This study was performed to determine whether vascular responses to ET-1 are altered by atherosclerosis. ET-1 (1 or 10 nmol) was injected intra-arterially into the perfused hind limb of normal cynomolgus monkeys and monkeys fed an atherogenic diet for 19 months. We calculated the resistance of the total limb and large arteries and estimated the resistance of the small vessels. The major finding was that ET-1 had minimal effects on large arteries in normal monkeys but produced pronounced constriction of large arteries in atherosclerotic monkeys. In both groups, ET-1 produced dilatation of small vessels at 1 nmol and constriction at 10 nmol. Indomethacin (6 mg/kg intravenously) did not affect the responses to ET-1 in normal or atherosclerotic monkeys. In summary, the major finding is that the constrictor responses of large arteries to ET-1 are potentiated by atherosclerosis.