Thromboxane receptor antagonism and synthase inhibition in cerebral ischemia

L. C. Pettigrew, R. J. Kryscio

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Thromboxane A2 (TXA2) is a proaggregatory vasoconstrictor that may suppress regional cerebral blood flow (rCBF) during postischemic hypoperfusion. This study was undertaken to determine if rCBF could be elevated by postischemic treatment with a TXA2 receptor antagonist, SQ29,548, given alone or in combination with 1-benzylimidazole (1-BI), a thromboxane synthase inhibitor. Wistar rats were subjected to 30 min of reversible forebrain ischemia and treated with SQ29,548 or an SQ29,548/1-BI combination during 60 min of reperfusion. Cerebral TXB2, the stable metabolite of TXA2, was 1.33 ± 0.91 ng mg brain protein-1 in animals treated with SQ29,548 and exposed to ischemia, compared to 1.15 ± 0.32 in ischemic controls (p = NS). Administration of SQ29,548/20 mg kg-1 1-BI reduced cerebral TXB2 to 0.20 ± 0.25 (p ≤ 0.01). Regional CBF was depressed significantly in ischemic controls compared to sham-ischemic animals (p ≤ 0.01 in all regions except for p ≤ 0.05 in diencephalon) and was not altered by treatment with SQ29,548. Rats given the SQ29,548/1-BI combination showed an overall increase in rCBF that did not reach statistical significance when compared to ischemic controls. However, rCBF in hippocampus and diencephalon of animals given the drug combination was significantly greater than in rats treated with SQ29,548 alone (p ≤ 0.05).

Original languageEnglish
Pages (from-to)211-217
Number of pages7
JournalProstaglandins, Leukotrienes and Essential Fatty Acids
Issue number3
StatePublished - Mar 1993

Bibliographical note

Funding Information:
This work was supportedb y NIH/NINDS Clinical Investigator Development Award NS01505 (L.C.P.), the Kentucky Affiliate of the American Heart Association, and the Research and Development Office, Medical Research Service, Department of Veterans Affairs. We are grateful to Martin L. Ogletree, PhD, and Charles D. Smith, MD, for their thoughtful comments. We thank Michael Adams and Rosa Earls for their technical assistancea nd express our appreciation to Carol Billingsley for typing the manuscript.

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology


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