Beteiligung von Tandem-Kalium-Kanälen in der durch ungesättigte Fettsäuren hervorgerufenen koronaren Vasodilatation
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Philipps-Universität Marburg
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Abstract
The monounsaturated fatty acid oleic acid and the polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid have been proposed to have a beneficial influence on human health. Although the vasodilatative effect of these substances has long been proven, the underlying mechanisms are still a subject of current research. It is further known that potassium channels are important regulators of coronary blood flow. However, little is known of the newly emerging subgroup of tandem-pore potassium channels, including the TREK and TASK channels, in this context. Using the isolated perfused guinea pig heart, we conducted a series of 88 experiments to quantify the vasodilatative effects of various lipids and to suggest a participation of tandem-pore potassium channels. Because of similar metabolism, we compared the effects of arachidonic acid and its amide, the endocannabinoid receptor agonist and TASK-1 channel blocker anandamide. We also conducted experiments using the local anesthetic bupivacaine, a blocker of TREK and TASK channels. The mean maximum reduction of coronary steady state perfusion pressure was measured: oleic acid 51.55 % , arachidonic acid 40.37 %, docosahexaenoic acid 47.95 %, eicosapentaenoic acid 47.40 %, anandamide 55.80 %, R-bupivacaine 72.11 %, S-Bupivacaine 39.85 %, racemic bupivacaine 70.65 %. Addition of the nitric oxide synthase inhibitor nitroarginin showed a reduction of this dilatative effect by the following factors: oleic acid 18.07 %, docosahexaenoic acid 13.10 %, eicosapentaenoic acid 7.55 %; yet only he effect for oleic acid was significant. The ATP-dependent potassium channel inhibitor glibenclamide did not show any effect on the vasodilatative effects of oleic, arachidonic, eicosapentaenoic, docosahexaenoic acids or R-bupivacaine, thus ruling out the commonly involved K-ATP channels. The COX inhibitor indomethacin also failed to show any reduction of vasodilation caused by arachidonic, docosahexaenoic, eicosapentaenoic acids or anandamide. Racemic bupivacaine and S-bupivacaine showed a biphasic effect consisting of a rapid vasodilation followed by a vasoconstriction, while R-bupivacaine only caused dilation. The maximum vasoconstrictory effect of S-bupivacaine was observed at a concentration of 25 µM, causing a 22.10 % rise of coronary perfusion pressure. This concentration of S-bupivacaine clearly reduced the vasodilation caused by docosahexaenoic and eicosapentaenoic acids. We hereby suggest a participation of tandem pore potassium channels in the coronary vasodilation caused by polyunsaturated fatty acids and a stereoselective inhibition of these channels by S-bupivacaine.
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Created: 2007Issued: 2007-02-19Updated: 2011-08-10
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
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DoctoralThesis
Keywords
TrekTraakPufaTaskTraakAnandamidAnandamidePufaTrekTask
DFG-subjects
KoronardurchblutungMeerschweinchenKaliumkanalKoronararterieFettsäurestoffwechselOmega-3-FettsäurePolyenfettsäurenHerzstoffwechsel
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610
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Burmester, Marko (132640058): Beteiligung von Tandem-Kalium-Kanälen in der durch ungesättigte Fettsäuren hervorgerufenen koronaren Vasodilatation. : Philipps-Universität Marburg 2007-02-19. DOI: https://doi.org/10.17192/z2007.0169.
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This item has been published with the following license: In Copyright