Epoxyeicosatrienoic acids, potassium channel blockers and endothelium-dependent hyperpolarization in the guinea-pig carotid artery. 1998

T Chataigneau, and M Félétou, and J Duhault, and P M Vanhoutte
Département de Diabétologie, Institut de Recherches Servier, Suresnes, France.

1. Using intracellular microelectrodes, we investigated the effects of 17-octadecynoic acid (17-ODYA) on the endothelium-dependent hyperpolarization induced by acetylcholine in the guinea-pig isolated internal carotid artery with endothelium. 2. In the presence of Nomega-nitro-L-arginine (L-NOARG, 100 microM) and indomethacin (5 microM) to inhibit nitric oxide synthase and cyclo-oxygenase, acetylcholine (1 microM) evoked an endothelium-dependent hyperpolarization which averaged -16.4 mV starting from a resting membrane potential of -56.8 mV. There was a negative correlation between the amplitude of the hyperpolarization and the absolute values of the resting membrane potential. 3. The acetylcholine-induced endothelium-dependent hyperpolarization was not altered by charybdotoxin (0.1 microM) or iberiotoxin (30 nM). It was partially but significantly reduced by apamin (0.5 microM) to -12.8+/-1.2 mV (n=10) or the combination of apamin plus iberiotoxin (-14.3+/-3.4mV, n=4). However, the combination of charybdotoxin and apamin abolished the hyperpolarization and under these conditions, acetylcholine evoked a depolarization (+ 7.1+/-3.7 mV, n = 8). 4. 17-ODYA (10 microM) produced a significant hyperpolarization of the resting membrane potential which averaged -59.6 mV and a partial but significant inhibition of the acetylcholine-induced endothelium-dependent hyperpolarization (-10.9 mV). 5. Apamin did not modify the effects of 17-ODYA but in the presence of charybdotoxin or iberiotoxin, 17-ODYA no longer influenced the resting membrane potential or the acetylcholine-induced hyperpolarization. 6. When compared to solvent (ethanol, 1% v/v), epoxyeicosatrienoic acids (EpETrEs) (5,6-, 8,9-, 11,12- and 14,15-EpETrE, 3 microM) did not affect the cell membrane potential and did not relax the guinea-pig isolated internal carotid artery. 7. These results indicate that, in the guinea-pig internal carotid artery, the involvement of metabolites of arachidonic acid through the cytochrome P450 pathway in endothelium-dependent hyperpolarization is unlikely. Furthermore, the hyperpolarization mediated by the endothelium-derived hyperpolarizing factor (EDHF) is probably not due to the opening of BK(Ca) channels.

UI MeSH Term Description Entries
D008297 Male Males
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D002339 Carotid Arteries Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. Arteries, Carotid,Artery, Carotid,Carotid Artery
D004576 Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Electromyogram,Surface Electromyography,Electromyograms,Electromyographies,Electromyographies, Surface,Electromyography, Surface,Surface Electromyographies
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005231 Fatty Acids, Unsaturated FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds. Fatty Acids, Polyunsaturated,Polyunsaturated Fatty Acid,Unsaturated Fatty Acid,Polyunsaturated Fatty Acids,Acid, Polyunsaturated Fatty,Acid, Unsaturated Fatty,Acids, Polyunsaturated Fatty,Acids, Unsaturated Fatty,Fatty Acid, Polyunsaturated,Fatty Acid, Unsaturated,Unsaturated Fatty Acids
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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