Hematoma-induced modification of cerebral microcirculation may involve endothelin-1 (ET-1) and lysophosphatedic acid (LPA)

M. A. Yakuhu, K. Liliom, G. J. Tigyi, C. W. Lcffler

Research output: Contribution to journalArticle

Abstract

ET-1 is increased by cerebral hematoma and inhibitors of ET-1 prevent hematoma-induced modification of cerebral arteriolar reactivity. However, the mechanism by which ET-1 contributes to hematoma-induced modifications of cerebral vascular reactivity is not known. We hypothesized that ET-1 injection intrathecally would 1) modify pial arteriolar reactivity to vasoactive agents similarly to hematoma and 2) increase CSF levels of LPA, a potential contributor to the altered cerebrovascular reactivity. Piglets received 3 ml injections containing either ET-1 (107 M) or aCSF over the left parietal cortex. Four days after injection, closed cranial windows were implanted over the injection area (a-chloralose anesthesia). Vascular reactivity to constrictor and dilator agents was examined. Constrictions to ET-1 (10-8 M), 5-HT (10-5 M), and NE (10"4 M) were potentiated; while dilations to PGE2 (10"5 M), iloprost (ID"8 M), and histamine (105 M) were attenuated. The ET-1 induced modifications were very similar to those following hematoma. ET-1 and LPA levels were increased while basal and stimulated cAMP levels were decreased 4 days following ET-1 injection. These results indicate that intrathecal injection of ET-1 mimics hematoma-induced modification of cerebral vascular reactivity and of LPA production. The mechanism(s) of ET-1 and hematoma-induced modifications may involve LPA, which could contribute to the loss of dilator responses by inhibition of cAMP production.

Original languageEnglish
JournalFASEB Journal
Volume10
Issue number3
Publication statusPublished - 1996

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Microcirculation
hematoma
endothelins
Endothelin-1
Hematoma
Acids
acids
injection
Injections
blood vessels
Blood Vessels
chloralose
Iloprost
Spinal Injections
Chloralose
Parietal Lobe
Granulocyte-Macrophage Colony-Stimulating Factor
histamine
Dinoprostone
serotonin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Hematoma-induced modification of cerebral microcirculation may involve endothelin-1 (ET-1) and lysophosphatedic acid (LPA). / Yakuhu, M. A.; Liliom, K.; Tigyi, G. J.; Lcffler, C. W.

In: FASEB Journal, Vol. 10, No. 3, 1996.

Research output: Contribution to journalArticle

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AU - Tigyi, G. J.

AU - Lcffler, C. W.

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