Blood-borne factors regulating microvascular constriction in the rat hippocampal slice

Previous work shows that blood serum contains a factor that elicits constriction of large cerebral arteries and may be responsible for cerebral vasospasm in subarachnoid hemorrhage patients. However, few studies have considered the action of potential spasmogens on intraparenchymal resistance vessels. We used a common preparation for neurophysiology, the rat hippocampal slice, to study penetrating arterioles and their response to a variety of potential vasoconstrictors. Dilute serum from clotted rat blood evoked profound microvascular constriction when applied to the slice, but plasma incubated with heparin to prevent coagulation was unable to do so. A variety of potential vasoconstrictor substances were tested to see if they could duplicate the effects of serum. Norepinephrine (10 microM), serotonin (one microM) and prostaglandin E2 (one nM) were ineffective in this regard. However, when a stable eicosanoid, thromboxane B2, was applied at a concentration achieved in the cerebrospinal fluid of subarachnoid hemorrhage patients, it duplicated a portion of the vasoconstriction produced by serum. It is concluded that thromboxane B2 may account for part of the spasmogenic property of serum and that unidentified molecules in the coagulation pathway may also play a role.