Effects of atherosclerosis on cerebral vessels: hemodynamic and morphometric studies

In this study hemodynamic and morphometric consequences of atherosclerosis were examined in cynomolgus monkeys. We tested the hypothesis that atherosclerosis augments cerebral vasoconstrictor responses to serotonin. We studied 8 normal and 8 atherosclerotic monkeys, which were fed an atherogenic diet for 17 months. Morphometric studies indicated marked intimal proliferation of extracranial carotid arteries, with only modest reduction in the vascular lumen, as atherosclerotic lesions were displaced outward. Cerebral blood flow was measured with microspheres and microvascular pressure was measured with a micropipette in pial arteries approximately 350 microns diameter. Intracarotid infusion of serotonin reduced microvascular pressure, which indicates constriction of large arteries upstream, but cerebral blood flow did not decrease. Serotonin produced a 2-fold greater reduction in cerebral microvascular pressure in atherosclerotic monkeys than in normal monkeys. Intracarotid histamine increased flow and hypocapnia reduced flow in both normal and atherosclerotic monkeys, without altering cerebral microvascular pressure. We conclude: First, atherosclerosis potentiates constrictor responses to serotonin in large cerebral arteries. Because platelets release serotonin when they aggregate, augmentation of responses by atherosclerosis may have implications for cerebral vascular responses during aggregation of platelets at carotid lesions. Second, despite marked proliferation of intima, atherosclerotic lesions are displaced outward during a prestenotic phase of the disease, so that the lumen is relatively well preserved.