Effects of leukotriene C4 on the cerebral microvasculature.

Abstract

Leukotriene C4, which is synthesized during cerebral ischemia, may contribute to disruption of the blood-brain barrier. The purpose of this study was to determine whether leukotriene C4 constricts cerebral arterioles and disrupts the blood-brain barrier. We used intravital fluorescent microscopy in hamsters and compared responses of vessels in the cerebrum with vessels in the cheek pouch. Increases in permeability of the cheek pouch and disruption of the blood-brain barrier were quantitated after superfusion with leukotriene C4 (0.3, 3.0, and 30 nM) by the formation of microvascular leaky sites. Changes in diameter of arterioles in the cheek pouch and cerebrum also were examined. In the cheek pouch, leukotriene C4 produced a dose-related decrease in diameter of arterioles (maximum = 40 +/- 8%; mean +/- SE) and an increase in microvascular permeability (maximum = 16 +/- 2 leaky sites). In contrast, in the cerebrum, leukotriene C4 produced only modest constriction of arterioles (maximum = 12 +/- 5%) and minimal disruption of the blood-brain barrier (maximum = 2 +/- 1 leaky sites). Thus the findings indicate that leukotriene C4, in contrast to its potent vasoconstrictor effects and increase in permeability in the hamster cheek pouch, produces only modest cerebral vasoconstriction and minimal disruption of the blood-brain barrier.