EFFECTS OF ATHEROSCLEROSIS AND REGRESSION ON VASCULAR-RESPONSES TO PRODUCTS OF ACTIVATED PLATELETS IN PRIMATES

We aggregated human platelets in vitro and examined vascular responses to injection of the supernatant in atherosclerotic primates. Platelets were washed, suspended, and aggregated with thrombin. Thrombin was then inactivated with D-Phe-Pro-ArgCH2Cl, and the suspension was centrifuged. The supernatant was injected intra-arterially into the perfused hindlimb within 30 s after aggregation of platelets. We studied normal cynomolgus monkeys, atherosclerotic monkeys that were fed atherogenic diet for 18 mo, and regression monkeys that were fed an atherogenic diet for 18 mo followed by a normal diet for 20 mo. Products of activated human platelets produced vasodilation in normal monkeys, as effects of platelet-derived vasodilators (presumably adenine nucleotides) may override platelet vasoconstrictor products. Vasodilator responses to platelet products were impaired in atherosclerotic monkeys, probably as a result of endothelial dysfunction. Regression of atherosclerosis restored vasodilator responses to platelet products toward normal. These data suggest that the predominant response to human platelet products is vasodilatation. Atherosclerosis impairs vasodilator responses to human platelet products, and regression of atherosclerosis restores responses toward normal.