Isoprostanes: Free Radical–Generated Prostaglandins With Constrictor Effects on Cerebral Arterioles

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Abstract
Background and Purpose Isoprostanes are generated by cyclooxygenase-independent free radical attack of arachidonic acid and are potent constrictors of the peripheral vasculature. Traumatic brain injury stimulates oxygen radical production and is associated with cerebral blood flow reduction. However, no specific vasoconstrictor has been identified as the cause of posttraumatic blood flow reduction. The purpose of this study was to determine whether isoprostanes constrict cerebral arterioles. Methods The effects of 10 −9 to 10 −5 mol/L 8-iso-prostaglandin F 2α (8-iso-PGF 2α ), 8-iso-prostaglandin E 2 (8-iso-PGE 2 ), and prostaglandin F 2α (PGF 2α ) on pial arteriolar diameter were measured in anesthetized rats using a closed cranial window and in vivo microscopy. Results All prostanoids produced vasoconstriction. Of these, 8-iso-PGF 2α produced the greatest vasoconstriction (34%±2), followed by 8-iso-PGE 2 (25%±4) and PGF 2α (20%±2). After six cerebrospinal fluid washouts of the cranial window, both 8-iso-PGF 2α – and 8-iso-PGE 2 –treated vessels remained slightly constricted, whereas the PGF 2α -treated vessels returned to control diameter. Coapplication of the semiselective thromboxane A 2 /prostaglandin H 2 receptor antagonist SQ29548 completely blocked the vasoconstriction induced by 8-iso-PGF 2α and 8-iso-PGE 2 . Conclusions Isoprostanes are potent constrictors of cerebral arterioles and appear to act at a receptor that is similar to the thromboxane A 2 /prostaglandin H 2 receptor. Isoprostanes may play a role in the reduction of cerebral blood flow that occurs after brain injury and subsequent oxygen radical production.