Effects of a 20-HETE antagonist and agonists on cerebral vascular tone

Ming Yu, Liana Cambj-Sapunar, Franz Kehl, Kristopher G. Maier, Kazuhiko Takeuchi, Noriyuki Miyata, Tsuyoshi Ishimoto, L. Manmohan Reddy, John R. Falck, Debebe Gebremedhin, David R. Harder, Richard J. Roman

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

This study examined the effects of a 20-hydroxyeicosatetraenoic acid (20-HETE) antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (WIT002) and two agonists, 4-amino-N-(20-hydroxy-eicosa-5(Z),14(Z)-dienoyl) benzenesulfonamide (ABSA) and 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid (WIT003), on the diameter of rat middle cerebral arteries in vitro and on cerebral blood flow in vivo. WIT003, ABSA and 20-HETE all had a similar effect to reduce the diameter of the middle cerebral artery by 26%. WIT003 and 20-HETE both increased intracellular Ca2+ concentration ([Ca2+]i) in vascular smooth muscle cells isolated from the middle cerebral artery. In contrast, WIT002 had no effect on the basal diameter of the middle cerebral artery but it attenuated the vasoconstrictor responses and the rise in [Ca2+] i in vascular smooth muscle cells following administration of 20-HETE and 5-hydroxytryptamine (5-HT). WIT003 partially restored the vasoconstrictor response to 5-HT in the middle cerebral artery after administration of an inhibitor of the endogenous synthesis of 20-HETE. Infusion of the 20-HETE agonists, WIT003 and ABSA, into cisterna magna of rats reduced baseline cerebral blood flow by 20%, whereas administration of the 20-HETE antagonist, WIT002, had no effect. Intracisternal injection of WIT002 attenuated the fall in cerebral blood flow following injection of blood into the cisterna magna, whereas administration of the 20-HETE agonist, ABSA, potentiated this response. These findings indicate that the 20-HETE agonists, WIT003 and ABSA, increase cerebral vascular tone both in vivo and in vitro and suggest blocking the vasoconstrictor actions of 20-HETE may be useful to prevent the acute fall in cerebral blood flow following subarachnoid hemorrhage.

Original languageEnglish (US)
Pages (from-to)297-306
Number of pages10
JournalEuropean Journal of Pharmacology
Volume486
Issue number3
DOIs
StatePublished - Feb 23 2004

Fingerprint

Blood Vessels
Cerebrovascular Circulation
Middle Cerebral Artery
Vasoconstrictor Agents
Cisterna Magna
Vascular Smooth Muscle
Smooth Muscle Myocytes
Serotonin
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Injections
Subarachnoid Hemorrhage

Keywords

  • 20-HETE
  • Agonist
  • Antagonist
  • Middle cerebral artery
  • Subarachnoid hemorrhage

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Yu, M., Cambj-Sapunar, L., Kehl, F., Maier, K. G., Takeuchi, K., Miyata, N., ... Roman, R. J. (2004). Effects of a 20-HETE antagonist and agonists on cerebral vascular tone. European Journal of Pharmacology, 486(3), 297-306. https://doi.org/10.1016/j.ejphar.2004.01.009

Effects of a 20-HETE antagonist and agonists on cerebral vascular tone. / Yu, Ming; Cambj-Sapunar, Liana; Kehl, Franz; Maier, Kristopher G.; Takeuchi, Kazuhiko; Miyata, Noriyuki; Ishimoto, Tsuyoshi; Reddy, L. Manmohan; Falck, John R.; Gebremedhin, Debebe; Harder, David R.; Roman, Richard J.

In: European Journal of Pharmacology, Vol. 486, No. 3, 23.02.2004, p. 297-306.

Research output: Contribution to journalArticle

Yu, M, Cambj-Sapunar, L, Kehl, F, Maier, KG, Takeuchi, K, Miyata, N, Ishimoto, T, Reddy, LM, Falck, JR, Gebremedhin, D, Harder, DR & Roman, RJ 2004, 'Effects of a 20-HETE antagonist and agonists on cerebral vascular tone', European Journal of Pharmacology, vol. 486, no. 3, pp. 297-306. https://doi.org/10.1016/j.ejphar.2004.01.009
Yu M, Cambj-Sapunar L, Kehl F, Maier KG, Takeuchi K, Miyata N et al. Effects of a 20-HETE antagonist and agonists on cerebral vascular tone. European Journal of Pharmacology. 2004 Feb 23;486(3):297-306. https://doi.org/10.1016/j.ejphar.2004.01.009
Yu, Ming ; Cambj-Sapunar, Liana ; Kehl, Franz ; Maier, Kristopher G. ; Takeuchi, Kazuhiko ; Miyata, Noriyuki ; Ishimoto, Tsuyoshi ; Reddy, L. Manmohan ; Falck, John R. ; Gebremedhin, Debebe ; Harder, David R. ; Roman, Richard J. / Effects of a 20-HETE antagonist and agonists on cerebral vascular tone. In: European Journal of Pharmacology. 2004 ; Vol. 486, No. 3. pp. 297-306.
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