Arachidonate dilates basilar artery by lipoxygenase-dependent mechanism and activation of K + channels

Frank M. Faraci, Christopher G. Sobey, Sophocles Chrissobolis, Donald D. Lund, Donald D. Heistad, Neal Lee Weintraub

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Dilatation of cerebral arterioles in response to arachidonic acid is dependent on activity of cyclooxygenase. In this study, we examined mechanisms that mediate dilatation of the basilar artery in response to arachidonate. Diameter of the basilar artery (baseline diameter = 216 ± 7 μm) (means ± SE) was measured using a cranial window in anesthetized rats. Arachidonic acid (10 and 100 μM) produced concentration-dependent vasodilatation that was not inhibited by indomethacin (10 mg/kg iv) or N G -nitro-L-arginine (100 μM) but was inhibited markedly by baicalein (10 μM) or nordihydroguaiaretic acid (NDGA; 10 μM), inhibitors of the lipoxygenase pathway. Dilatation of the basilar artery was also inhibited markedly by tetraethylammonium ion (TEA; 1 mM) or iberiotoxin (50 nM), inhibitors of calcium-dependent potassium channels. For example, 10 μM arachidonate dilated the basilar artery by 19 ± 7 and 1 ± 1% in the absence and presence of iberiotoxin, respectively. Measurements of membrane potential indicated that arachidonate produced hyperpolarization of the basilar artery that was blocked completely by TEA. Incubation with [ 3 H]arachidonic acid followed by reverse-phase and chiral HPLC indicated that the basilar artery produces relatively small quantities of prostanoids but large quantities of 12(S)-hydroxyeicosatetraenoic acid (12-S-HETE), a lipoxygenase product. Moreover, the production of 12-HETE was inhibited by baicalein or NDGA. These findings suggest that dilatation of the basilar artery in response to arachidonate is mediated by a product(s) of the lipoxygenase pathway, with activation of calcium-dependent potassium channels and hyperpolarization of vascular muscle.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume281
Issue number1 50-1
StatePublished - Oct 10 2001
Externally publishedYes

Fingerprint

Basilar Artery
Lipoxygenase
Dilatation
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Arachidonic Acid
Calcium-Activated Potassium Channels
Masoprocol
Lipoxygenase Inhibitors
Tetraethylammonium
Arterioles
Prostaglandin-Endoperoxide Synthases
Vasodilation
Indomethacin
Membrane Potentials
Prostaglandins
Blood Vessels
Arginine
High Pressure Liquid Chromatography
Muscles

Keywords

  • Calcium-activated potassium channels
  • Cyclooxygenase
  • Iberiotoxin
  • Membrane potential

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Arachidonate dilates basilar artery by lipoxygenase-dependent mechanism and activation of K + channels . / Faraci, Frank M.; Sobey, Christopher G.; Chrissobolis, Sophocles; Lund, Donald D.; Heistad, Donald D.; Weintraub, Neal Lee.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 281, No. 1 50-1, 10.10.2001.

Research output: Contribution to journalArticle

Faraci, Frank M. ; Sobey, Christopher G. ; Chrissobolis, Sophocles ; Lund, Donald D. ; Heistad, Donald D. ; Weintraub, Neal Lee. / Arachidonate dilates basilar artery by lipoxygenase-dependent mechanism and activation of K + channels In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2001 ; Vol. 281, No. 1 50-1.
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AU - Faraci, Frank M.

AU - Sobey, Christopher G.

AU - Chrissobolis, Sophocles

AU - Lund, Donald D.

AU - Heistad, Donald D.

AU - Weintraub, Neal Lee

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N2 - Dilatation of cerebral arterioles in response to arachidonic acid is dependent on activity of cyclooxygenase. In this study, we examined mechanisms that mediate dilatation of the basilar artery in response to arachidonate. Diameter of the basilar artery (baseline diameter = 216 ± 7 μm) (means ± SE) was measured using a cranial window in anesthetized rats. Arachidonic acid (10 and 100 μM) produced concentration-dependent vasodilatation that was not inhibited by indomethacin (10 mg/kg iv) or N G -nitro-L-arginine (100 μM) but was inhibited markedly by baicalein (10 μM) or nordihydroguaiaretic acid (NDGA; 10 μM), inhibitors of the lipoxygenase pathway. Dilatation of the basilar artery was also inhibited markedly by tetraethylammonium ion (TEA; 1 mM) or iberiotoxin (50 nM), inhibitors of calcium-dependent potassium channels. For example, 10 μM arachidonate dilated the basilar artery by 19 ± 7 and 1 ± 1% in the absence and presence of iberiotoxin, respectively. Measurements of membrane potential indicated that arachidonate produced hyperpolarization of the basilar artery that was blocked completely by TEA. Incubation with [ 3 H]arachidonic acid followed by reverse-phase and chiral HPLC indicated that the basilar artery produces relatively small quantities of prostanoids but large quantities of 12(S)-hydroxyeicosatetraenoic acid (12-S-HETE), a lipoxygenase product. Moreover, the production of 12-HETE was inhibited by baicalein or NDGA. These findings suggest that dilatation of the basilar artery in response to arachidonate is mediated by a product(s) of the lipoxygenase pathway, with activation of calcium-dependent potassium channels and hyperpolarization of vascular muscle.

AB - Dilatation of cerebral arterioles in response to arachidonic acid is dependent on activity of cyclooxygenase. In this study, we examined mechanisms that mediate dilatation of the basilar artery in response to arachidonate. Diameter of the basilar artery (baseline diameter = 216 ± 7 μm) (means ± SE) was measured using a cranial window in anesthetized rats. Arachidonic acid (10 and 100 μM) produced concentration-dependent vasodilatation that was not inhibited by indomethacin (10 mg/kg iv) or N G -nitro-L-arginine (100 μM) but was inhibited markedly by baicalein (10 μM) or nordihydroguaiaretic acid (NDGA; 10 μM), inhibitors of the lipoxygenase pathway. Dilatation of the basilar artery was also inhibited markedly by tetraethylammonium ion (TEA; 1 mM) or iberiotoxin (50 nM), inhibitors of calcium-dependent potassium channels. For example, 10 μM arachidonate dilated the basilar artery by 19 ± 7 and 1 ± 1% in the absence and presence of iberiotoxin, respectively. Measurements of membrane potential indicated that arachidonate produced hyperpolarization of the basilar artery that was blocked completely by TEA. Incubation with [ 3 H]arachidonic acid followed by reverse-phase and chiral HPLC indicated that the basilar artery produces relatively small quantities of prostanoids but large quantities of 12(S)-hydroxyeicosatetraenoic acid (12-S-HETE), a lipoxygenase product. Moreover, the production of 12-HETE was inhibited by baicalein or NDGA. These findings suggest that dilatation of the basilar artery in response to arachidonate is mediated by a product(s) of the lipoxygenase pathway, with activation of calcium-dependent potassium channels and hyperpolarization of vascular muscle.

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