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(Stroke. 1997;28:844-849.)
© 1997 American Heart Association, Inc.

Articles

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

Stuart W. Hoffman, PhD; Sandra Moore, BS Earl F. Ellis, PhD

From the Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University (Richmond).

Correspondence to Dr Stuart W. Hoffman, Department of Pharmacology and Toxicology, Medical College of Virginia, PO Box 980613, 410 N 12th St, Room 754, Richmond, VA 23298. E-mail swhoffman{at}gems.vcu.edu

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 F₂ (8-iso-PGF₂), 8-iso-prostaglandin E₂ (8-iso-PGE₂), and prostaglandin F₂ (PGF₂) 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-PGF₂ produced the greatest vasoconstriction (34%±2), followed by 8-iso-PGE₂ (25%±4) and PGF₂ (20%±2). After six cerebrospinal fluid washouts of the cranial window, both 8-iso-PGF₂– and 8-iso-PGE₂–treated vessels remained slightly constricted, whereas the PGF₂-treated vessels returned to control diameter. Coapplication of the semiselective thromboxane A₂/prostaglandin H₂ receptor antagonist SQ29548 completely blocked the vasoconstriction induced by 8-iso-PGF₂ and 8-iso-PGE₂.

Conclusions Isoprostanes are potent constrictors of cerebral arterioles and appear to act at a receptor that is similar to the thromboxane A₂/prostaglandin H₂ receptor. Isoprostanes may play a role in the reduction of cerebral blood flow that occurs after brain injury and subsequent oxygen radical production.

Key Words: brain injuries • cerebral circulation • cerebral ischemia • lipid peroxidation • oxygen radical • rats

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