TY - JOUR
T1 - Bradykinin-induced, endothelium-dependent responses in porcine coronary arteries
T2 - Involvement of potassium channel activation and epoxyeicosatrienoic acids
AU - Weston, Arthur H.
AU - Félétou, Michel
AU - Vanhoutte, Paul M.
AU - Falck, J R
AU - Campbell, William B.
AU - Edwards, Gillian
PY - 2005/7
Y1 - 2005/7
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.
KW - 11,12-EET
KW - 14,15-EET
KW - 14,15-EEZE
KW - 14,15-EEZE-mSI
KW - 5,6-EET
KW - Bradykinin
KW - EDHF
KW - Endothelium-dependent hyperpolarization
KW - Porcine coronary artery
KW - Substance P
UR - http://www.scopus.com/inward/record.url?scp=23044461193&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23044461193&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0706256
DO - 10.1038/sj.bjp.0706256
M3 - Article
C2 - 15895105
AN - SCOPUS:23044461193
SN - 0007-1188
VL - 145
SP - 775
EP - 784
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 6
ER -