Bradykinin-induced, endothelium-dependent responses in porcine coronary arteries: involvement of potassium channel activation and epoxyeicosatrienoic acids.

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作者：

A Weston，M Félétou，P Vanhoutte，J Falck，W Campbell，G Edwards

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摘要：

1 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. 2 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 M TRAM-39 (2-(2-chlorophenyl)-2,2-diphenylacetonitrile) plus 100 n M apamin (leaving an iberiotoxin-sensitive component), whereas the response to substance P was abolished. 3 After gap junction blockade with HEPES, ( N -(2-hydroxyethyl)piperazine- N '-(2-ethanesulphonic acid)) hyperpolarization of the endothelium by 100 n M 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 n M bradykinin were antagonized by the EET antagonist, 14,15-EEZE (14,15-epoxyeicosa-5(Z)-enoic acid) (10 M ), 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. 4 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. British Journal of Pharmacology (2005) 145 , 775784. doi: [DOI link]

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Article

DOI：

10.1038/sj.bjp.0706256

被引量：

264

年份：

2005