Bradykinin-induced, endothelium-dependent responses in porcine coronary arteries

Involvement of potassium channel activation and epoxyeicosatrienoic acids

Arthur H. Weston, Michel Félétou, Paul M. Vanhoutte, J R Falck, William B. Campbell, Gillian Edwards

Research output: Contribution to journalArticle

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Abstract

In coronary arteries, bradykinin opens endothelial intermediate- and small-conductance Ca 2+-sensitive K + channels (IK Ca and SK Ca) and, additionally, releases epoxyeicosatrienoic acids (EETs) from the endothelium. To clarify the involvement of these pathways in endothelium-dependent myocyte hyperpolarization, bradykinin-induced electrical changes in endothelial cells and myocytes of porcine coronary arteries (following nitric oxide (NO) synthase and cyclooxygenase inhibition) were measured using sharp microelectrodes. Hyperpolarization of endothelial cells by bradykinin (27.0±0.9 mV, n = 4) was partially inhibited (74%) by blockade of IK Ca and SK Ca channels using 10 μM TRAM-39 (2-(2-chlorophenyl)-2,2- diphenylacetonitrile) plus 100 nM apamin (leaving an iberiotoxin-sensitive component), whereas the response to substance P was abolished. After gap junction blockade with HEPES, (N-(2-hydroxyethyl)piperazine-N′-(2- ethanesulphonic acid)) hyperpolarization of the endothelium by 100 nM bradykinin was abolished by TRAM-39 plus apamin, whereas myocyte hyperpolarization still occurred (12.9 ± 1.0 mV, n = 4). The residual hyperpolarizations to 100 nM bradykinin were antagonized by the EET antagonist, 14,15-EEZE (14,15-epoxyeicosa-5(Z)-enoic acid) (10 μM), and abolished by iberiotoxin. Bradykinin-induced myocyte hyperpolarizations were also reduced by 14,15-EEZE-mSI (14,15-EEZE-methylsulfonylimide) (5,6- and 14,15-EET antagonist), whereas those to exogenous 11,12-EET were unaffected. These data show that bradykinin-induced hyperpolarization of endothelial cells (due to the opening of IK Ca and SK Ca channels) is electrotonically transferred to the myocytes via gap junctions. Bradykinin (but not substance P) also hyperpolarizes myocytes by a mechanism (independent of endothelial cell hyperpolarization) which involves endothelial cell production of EETs (most likely 14,15- and/or 11,12-EET). These open endothelial IK Ca and SK Ca channels and also activate large-conductance calcium-sensitive K + channels (BK Ca) on the surrounding myocytes.

Original languageEnglish (US)
Pages (from-to)775-784
Number of pages10
JournalBritish Journal of Pharmacology
Volume145
Issue number6
DOIs
StatePublished - Jul 2005

Fingerprint

Potassium Channels
Bradykinin
Endothelium
Coronary Vessels
Muscle Cells
Swine
Acids
Endothelial Cells
Apamin
Gap Junctions
Substance P
Large-Conductance Calcium-Activated Potassium Channels
HEPES
Microelectrodes
Prostaglandin-Endoperoxide Synthases
Nitric Oxide Synthase
Calcium

Keywords

  • 11,12-EET
  • 14,15-EET
  • 14,15-EEZE
  • 14,15-EEZE-mSI
  • 5,6-EET
  • Bradykinin
  • EDHF
  • Endothelium-dependent hyperpolarization
  • Porcine coronary artery
  • Substance P

ASJC Scopus subject areas

  • Pharmacology

Cite this

Bradykinin-induced, endothelium-dependent responses in porcine coronary arteries : Involvement of potassium channel activation and epoxyeicosatrienoic acids. / Weston, Arthur H.; Félétou, Michel; Vanhoutte, Paul M.; Falck, J R; Campbell, William B.; Edwards, Gillian.

In: British Journal of Pharmacology, Vol. 145, No. 6, 07.2005, p. 775-784.

Research output: Contribution to journalArticle

Weston, Arthur H. ; Félétou, Michel ; Vanhoutte, Paul M. ; Falck, J R ; Campbell, William B. ; Edwards, Gillian. / Bradykinin-induced, endothelium-dependent responses in porcine coronary arteries : Involvement of potassium channel activation and epoxyeicosatrienoic acids. In: British Journal of Pharmacology. 2005 ; Vol. 145, No. 6. pp. 775-784.
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T2 - Involvement of potassium channel activation and epoxyeicosatrienoic acids

AU - Weston, Arthur H.

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AU - Campbell, William B.

AU - Edwards, Gillian

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N2 - In coronary arteries, bradykinin opens endothelial intermediate- and small-conductance Ca 2+-sensitive K + channels (IK Ca and SK Ca) and, additionally, releases epoxyeicosatrienoic acids (EETs) from the endothelium. To clarify the involvement of these pathways in endothelium-dependent myocyte hyperpolarization, bradykinin-induced electrical changes in endothelial cells and myocytes of porcine coronary arteries (following nitric oxide (NO) synthase and cyclooxygenase inhibition) were measured using sharp microelectrodes. Hyperpolarization of endothelial cells by bradykinin (27.0±0.9 mV, n = 4) was partially inhibited (74%) by blockade of IK Ca and SK Ca channels using 10 μM TRAM-39 (2-(2-chlorophenyl)-2,2- diphenylacetonitrile) plus 100 nM apamin (leaving an iberiotoxin-sensitive component), whereas the response to substance P was abolished. After gap junction blockade with HEPES, (N-(2-hydroxyethyl)piperazine-N′-(2- ethanesulphonic acid)) hyperpolarization of the endothelium by 100 nM bradykinin was abolished by TRAM-39 plus apamin, whereas myocyte hyperpolarization still occurred (12.9 ± 1.0 mV, n = 4). The residual hyperpolarizations to 100 nM bradykinin were antagonized by the EET antagonist, 14,15-EEZE (14,15-epoxyeicosa-5(Z)-enoic acid) (10 μM), and abolished by iberiotoxin. Bradykinin-induced myocyte hyperpolarizations were also reduced by 14,15-EEZE-mSI (14,15-EEZE-methylsulfonylimide) (5,6- and 14,15-EET antagonist), whereas those to exogenous 11,12-EET were unaffected. These data show that bradykinin-induced hyperpolarization of endothelial cells (due to the opening of IK Ca and SK Ca channels) is electrotonically transferred to the myocytes via gap junctions. Bradykinin (but not substance P) also hyperpolarizes myocytes by a mechanism (independent of endothelial cell hyperpolarization) which involves endothelial cell production of EETs (most likely 14,15- and/or 11,12-EET). These open endothelial IK Ca and SK Ca channels and also activate large-conductance calcium-sensitive K + channels (BK Ca) on the surrounding myocytes.

AB - In coronary arteries, bradykinin opens endothelial intermediate- and small-conductance Ca 2+-sensitive K + channels (IK Ca and SK Ca) and, additionally, releases epoxyeicosatrienoic acids (EETs) from the endothelium. To clarify the involvement of these pathways in endothelium-dependent myocyte hyperpolarization, bradykinin-induced electrical changes in endothelial cells and myocytes of porcine coronary arteries (following nitric oxide (NO) synthase and cyclooxygenase inhibition) were measured using sharp microelectrodes. Hyperpolarization of endothelial cells by bradykinin (27.0±0.9 mV, n = 4) was partially inhibited (74%) by blockade of IK Ca and SK Ca channels using 10 μM TRAM-39 (2-(2-chlorophenyl)-2,2- diphenylacetonitrile) plus 100 nM apamin (leaving an iberiotoxin-sensitive component), whereas the response to substance P was abolished. After gap junction blockade with HEPES, (N-(2-hydroxyethyl)piperazine-N′-(2- ethanesulphonic acid)) hyperpolarization of the endothelium by 100 nM bradykinin was abolished by TRAM-39 plus apamin, whereas myocyte hyperpolarization still occurred (12.9 ± 1.0 mV, n = 4). The residual hyperpolarizations to 100 nM bradykinin were antagonized by the EET antagonist, 14,15-EEZE (14,15-epoxyeicosa-5(Z)-enoic acid) (10 μM), and abolished by iberiotoxin. Bradykinin-induced myocyte hyperpolarizations were also reduced by 14,15-EEZE-mSI (14,15-EEZE-methylsulfonylimide) (5,6- and 14,15-EET antagonist), whereas those to exogenous 11,12-EET were unaffected. These data show that bradykinin-induced hyperpolarization of endothelial cells (due to the opening of IK Ca and SK Ca channels) is electrotonically transferred to the myocytes via gap junctions. Bradykinin (but not substance P) also hyperpolarizes myocytes by a mechanism (independent of endothelial cell hyperpolarization) which involves endothelial cell production of EETs (most likely 14,15- and/or 11,12-EET). These open endothelial IK Ca and SK Ca channels and also activate large-conductance calcium-sensitive K + channels (BK Ca) on the surrounding myocytes.

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KW - 5,6-EET

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KW - Endothelium-dependent hyperpolarization

KW - Porcine coronary artery

KW - Substance P

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