Isoprostanes: free radical-generated prostaglandins with constrictor effects on cerebral arterioles.
OBJECTIVE
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 alpha (8-iso-PGF2 alpha), 8-iso-prostaglandin E2 (8-iso-PGE2), and prostaglandin F2 alpha (PGF2 alpha) 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 alpha produced the greatest vasoconstriction (34% +/- 2), followed by 8-iso-PGE2 (25% +/- 4) and PGF2 alpha (20% +/- 2). After six cerebrospinal fluid washouts of the cranial window, both 8-iso-PGF2 alpha- and 8-iso-PGE2-treated vessels remained slightly constricted, whereas the PGF2 alpha-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 alpha 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.
Hoffman
S W
SW
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University Richmond 23298, USA. swhoffman@gems.vcu.edu
Moore
S
S
Ellis
E F
EF
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; D005609:Free Radicals / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D028421:Isoprostanes; D008297:Male; D010841:Pia Mater / Q000098:blood supply*; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D006834:Hydrazines; D028421:Isoprostanes; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; C045749:SQ 29548; D015237:Dinoprost; D015232:Dinoprostone; C011987:8-isoprostaglandin E2