12-Lipoxygenase in porcine coronary microcirculation: Implications for coronary vasoregulation

Martin H. Zink, Christine L. Oltman, Tong Lu, Prasad V.G. Katakam, Terry L. Kaduce, Hon Chi Lee, Kevin C. Dellsperger, Arthur A. Spector, Paul R. Myers, Neal L. Weintraub

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Noncyclooxygenase metabolites of arachidonic acid (AA) have been proposed to mediate endothelium-dependent vasodilation in the coronary microcirculation. Therefore, we examined the formation and bioactivity of AA metabolites in porcine coronary (PC) microvascular endothelial cells and microvessels, respectively. The major noncyclooxygenase metabolite produced by microvascular endothelial cells was 12(S)-hydroxyeicosatetraenoic acid (HETE), a lipoxygenase product. 12(S)-HETE release was markedly increased by pretreatment with 13(S)-hydroperoxyoctadecadienoic acid but not by the reduced congener 13(S)-hydroxyoctadecadienoic acid, suggesting oxidative upregulation of 12(S)-HETE output. 12(S)-HETE produced potent relaxation and hyperpolarization of PC microvessels (EC50, expressed as -log[M] = 13.5 ± 0.5). Moreover, 12(S)-HETE potently activated large-conductance Ca2+-activated K+ currents in PC microvascular smooth muscle cells. In contrast, 12(S)-HETE was not a major product of conduit PC endothelial AA metabolism and did not exhibit potent bioactivity in conduit PC arteries. We suggest that, in the coronary microcirculation, 12(S)-HETE can function as a potent hyperpolarizing vasodilator that may contribute to endothelium-dependent relaxation, particularly in the setting of oxidative stress.

Original languageEnglish (US)
Pages (from-to)H693-H704
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number2 49-2
DOIs
StatePublished - Feb 2001
Externally publishedYes

Keywords

  • 12(S)-hydroxyeicosatetraenoic acid
  • Arachidonic acid
  • Hyperpolarization
  • Oxidative stress
  • Vasodi lation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Zink, M. H., Oltman, C. L., Lu, T., Katakam, P. V. G., Kaduce, T. L., Lee, H. C., Dellsperger, K. C., Spector, A. A., Myers, P. R., & Weintraub, N. L. (2001). 12-Lipoxygenase in porcine coronary microcirculation: Implications for coronary vasoregulation. American Journal of Physiology - Heart and Circulatory Physiology, 280(2 49-2), H693-H704. https://doi.org/10.1152/ajpheart.2001.280.2.h693