Effects of leukotrienes C4, D4, and E4 on cerebral arteries of newborn pigs

We examined effects of topical application of leukotrienes (LT) C4, D4, and E4 on cerebral arteries of newborn pigs in vivo. Diameters of pial arteries were measured using a cranial window method during application of artificial cerebrospinal fluid without drug, and cerebrospinal fluid containing LT C4, D4, and E4 (1, 10, 100, 1000, and 5000 ng/ml). Control diameters ranged from 51-345 micron. All three LT constricted pial arteries in a dose-dependent manner, with a threshold for detectable response at 10 ng/ml (7 +/- 3% for LTD4). The magnitude of constrictor response at the highest dose was 23 +/- 3% for LTC4, 17 +/- 2% for LTD4, and 17 +/- 3% for LTE4. The specific receptor antagonist FPL 55712 blocked the constrictor response to LT. We conclude that LT are potent constrictors of cerebral arteries in newborn pigs.