Leukotriene D4 and the cerebral vasculature in vivo and in vitro

The effects of leukotriene D4 (LTD4), a component of the slow reacting substance of anaphylaxis (SRS-A), and the putative SRS-A antagonist FPL 55712 were studied on cerebral arteries in vivo and in vitro. Intracarotid injection of LTD4 (1-15 nmols/kg) into the cerebral vasculature of the anaesthetised rat constricted internal and external carotid, facio-lingual and stapedial arteries for up to 40 minutes. LTD4 at 3 nmol/kg caused a slight fall in heart rate, and at 6 and 12 nmol/kg, an increase in diastolic (but not systolic) blood pressure was observed. In some experiments, constriction was followed by dilatation (possibly due to enhanced prostacyclin synthesis). FPL 55712 (0.3 to 30 nmols/kg) injected in the same manner caused both constriction and dilatation of rat cerebral arteries. In vitro experiments were performed on isolated human intracranial arteries (basilar, vertebral and Circle of Willis) obtained at autopsy, and on the isolated rat stomach fundus. LTD4 (2 x 10(-9) to 2 x 10(-7) M) caused sustained contractions of isolated human intracranial arteries. FPL 55712 (up to 4 x 10(-7) M) failed to antagonise the vasoconstrictor effects of LTD4, and higher concentrations (8 x 10(-6) to 8 x 10(-5) M) directly relaxed cerebral arteries. In contrast, FPL 55712 (2 x 10(-8) M) was a competitive antagonist of the contractile effects of LTD4 on the isolated rat fundus. This data suggests that the cerebral arterial leukotriene receptor differs from the peripheral smooth muscle receptor typified by the guinea-pig ileum and rat fundus preparations. Furthermore, leukotrienes may be involved in pathological vasoconstriction of various vascular beds after immunological reaction and trauma.