Effect of Leukotrienes, 12-HETE, Histamine, Bradykinin, and 5-Hydroxytryptamine on in vivo Rabbit Cerebral Arteriolar Diameter

Abstract

To determine the possible role that leukotrienes (LTs) may play in the regulation of cerebral blood flow, the responses of cerebral arterioles to LTs and 12-hydroxyeicosatetraenoic acid (12-HETE) were studied in vivo in rabbits equipped with a cranial window for direct observation of the microcirculation. Topical application of LTC, LTD₄, or 12-HETE (1.6 × 10⁻⁹–3.1 × 10⁻⁶ M) neither constricted nor dilated the pial arteries. LTB₄ produced only a 5% vasoconstriction at 3.0 × 10⁻⁶ M. However, bradykinin induced dose-dependent arteriolar vasodilation and histamine and 5-hydroxytryptamine induced dose-dependent arteriolar vasoconstriction. Although some LTs have potent vasoconstrictor activity in peripheral tissues and 5-lipoxygenase products have been hypothesized to be mediators of vasospasm after subarachnoid hemorrhage, LTB₄, LTC₄, LTD₄, and 12-HETE apparently are unable to induce significant constriction of the cerebral arterioles in the anesthetized rabbit.