Effect of thromboxane synthase inhibition on eicosanoid levels and blood flow in ischemic rat brain.
Reperfusion of ischemic brain is associated with production of thromboxane A2 (TXA2), a proaggregatory vasoconstrictor. We used an animal model of transient forebrain ischemia to study the effects of 1-benzylimidazole (1-BI), a selective inhibitor of thromboxane synthase, upon cerebral eicosanoid levels and cerebral blood flow. Male Wistar rats were subjected to 30 minutes of four-vessel occlusion. The mean +/- SEM brain level of TXB2, the stable metabolite of TXA2, determined after 60 minutes of reperfusion was 101 +/- 20 pg/mg brain protein in five ischemic control rats. Infusion of 10 micrograms/g 1-BI reduced mean +/- SEM cerebral TXB2 concentration to 11 +/- 3 pg/mg brain protein in five rats (p less than or equal to 0.002). Mean +/- SEM hemispheric cerebral blood flow measured in four ischemic control rats after 60 minutes of reperfusion was 42 +/- 9 ml/100 g brain/min compared with 104 +/- 13 ml/100 g brain/min in three 1-BI-treated rats (p less than or equal to 0.001). Mean +/- SEM hippocampal blood flow in four ischemic control rats after 60 minutes of reperfusion was 51 +/- 14 ml/100 g brain/min compared with 125 +/- 25 ml/100 g brain/min in three 1-BI-treated rats (p less than or equal to 0.04). We conclude that selective inhibition of thromboxane synthase may alleviate ischemic brain damage by reducing cerebral TXA2 concentrations and elevating cerebral blood flow.
Pettigrew
L C
LC
Department of Neurology, University of Texas Medical School, Houston 77225.
Grotta
J C
JC
Rhoades
H M
HM
Wu
K K
KK
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000097:blood / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004537:Eicosanoic Acids / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004537:Eicosanoic Acids; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase