ISOPROSTANES - FREE RADICAL-GENERATED PROSTAGLANDINS WITH CONSTRICTOREFFECTS ON CEREBRAL ARTERIOLES

Background and Purpose Isoprostanes are generated by cyclooxygenase-in dependent free radical attack of arachidonic acid and are potent const rictors of the peripheral vasculature. Traumatic brain injury stimulat es oxygen radical production and is associated with cerebral blood flo w reduction. However. no specific vasoconstrictor has been identified as the cause of posttraumatic blood flow reduction. The purpose of thi s study was to determine whether isoprostanes constrict cerebral arter ioles. Methods The effects of 10(-9) to 10(-5) mol/L 8-iso-prostagland in F-2 alpha (8-iso-PGF(2 alpha)), S-iso-prostaglandin E(2) (8-isol-PG E(2)), and prostaglandin F-2 alpha (PGF(2 alpha)) on pial arteriolar d iameter were measured in anesthetized rats using a closed cranial wind ow and in vivo microscopy. Results All prostanoids produced vasoconstr iction. Of these, 8-iso-PGF(2 alpha) produced the greatest vasoconstri ction (34% +/- 2), followed by 8-iso-PGE(2) (25% +/- 4) and PGF(2 alph a) (20% +/- 2). After six cerebrospinal fluid washouts of the cranial window, both 8-iso-PGF(2 alpha),- and 8-iso-PGE(2)-treated vessels rem ained slightly constricted, whereas tile PGF(2a)-treated vessels retur ned to control diameter, Coapplication of the semiselective thromboxan e A(2)/prostaglandin H-2 receptor antagonist SQ29548 completely blocke d the vasoconstriction induced by 8-iso-PGF(2a) and 8-iso-PGE(2). Conc lusions Isoprostanes are potent constrictors of cerebral arterioles an d 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 reduct ion of cerebral blood flow that occurs after brain injury and subseque nt oxygen radical production.