Cerebral vasoconstrictor responses to serotonin after dietary treatment of atherosclerosis: implications for transient ischemic attacks

Serotonin, which is released when platelets aggregate at carotid lesions, may contribute to cerebral ischemia. Our goal was to test the hypothesis that dietary treatment of atherosclerosis reverses the augmented cerebral vasoconstrictor response to serotonin. We studied normal cynomolgus monkeys, atherosclerotic monkeys, and atherosclerotic monkeys that were fed a normal (regression) diet for 18 months. Morphometric studies indicated that the regression diet reduced intimal area in the carotid arteries by about 50-75%. Cerebral blood flow was measured with microspheres, and microvascular pressure was measured with a micropipette in pial arteries that were approximately 300 micron in diameter. Values for cerebral blood flow and arteriolar pressure were used to calculate resistance of large cerebral arteries (greater than 300 micron diameter). Infusion of serotonin produced a modest increase in the resistance of large cerebral arteries in normal monkeys. Vasoconstrictor responses to serotonin were increased more than fivefold in atherosclerotic monkeys. The major finding of the study is that dietary treatment of atherosclerosis abolishes augmented cerebral responses to serotonin.