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The Unexpected Role of Calcium‐Activated Potassium Channels: Limitation of NO‐Induced Arterial Relaxation
BACKGROUND: Multiple studies have shown that an NO‐induced activation of vascular smooth muscle BK channels contributes to the NO‐evoked dilation in many blood vessels. In vivo, NO is released continuously. NO attenuates vessel constrictions and, therefore, exerts an anticontractile effect. It is un...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907584/ https://www.ncbi.nlm.nih.gov/pubmed/29574460 http://dx.doi.org/10.1161/JAHA.117.007808 |
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author | Schmid, Johannes Müller, Bettina Heppeler, David Gaynullina, Dina Kassmann, Mario Gagov, Hristo Mladenov, Mitko Gollasch, Maik Schubert, Rudolf |
author_facet | Schmid, Johannes Müller, Bettina Heppeler, David Gaynullina, Dina Kassmann, Mario Gagov, Hristo Mladenov, Mitko Gollasch, Maik Schubert, Rudolf |
author_sort | Schmid, Johannes |
collection | PubMed |
description | BACKGROUND: Multiple studies have shown that an NO‐induced activation of vascular smooth muscle BK channels contributes to the NO‐evoked dilation in many blood vessels. In vivo, NO is released continuously. NO attenuates vessel constrictions and, therefore, exerts an anticontractile effect. It is unknown whether the anticontractile effect of continuously present NO is mediated by BK channels. METHODS AND RESULTS: This study tested the hypothesis that BK channels mediate the vasodilatory effect of continuously present NO. Experiments were performed on rat and mouse tail and rat saphenous arteries using isometric myography and FURA‐2 fluorimetry. Continuously present NO donors, as well as endogenous NO, attenuated methoxamine‐induced vasoconstrictions. This effect was augmented in the presence of the BK channel blocker iberiotoxin. Moreover, the contractile effect of iberiotoxin was reduced in the presence of NO donors. The effect of the NO donor sodium nitroprusside was abolished by an NO scavenger and by a guanylyl cyclase inhibitor. In addition, the effect of sodium nitroprusside was reduced considerably by a protein kinase G inhibitor, but was not altered by inhibition of H(2)S generation. Sodium nitroprusside attenuated the intracellular calcium concentration response to methoxamine. Furthermore, sodium nitroprusside strongly reduced methoxamine‐induced calcium influx, which depends entirely on L‐type calcium channels. It did not affect methoxamine‐induced calcium release. CONCLUSIONS: In summary, this study demonstrates the following: (1) continuously present NO evokes a strong anticontractile effect on rat and mouse arteries; (2) the iberiotoxin‐induced augmentation of the effect of NO is associated with an NO‐induced reduction of the effect of iberiotoxin; and (3) NO evoked a reduction of calcium influx via L‐type calcium channels. |
format | Online Article Text |
id | pubmed-5907584 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59075842018-05-01 The Unexpected Role of Calcium‐Activated Potassium Channels: Limitation of NO‐Induced Arterial Relaxation Schmid, Johannes Müller, Bettina Heppeler, David Gaynullina, Dina Kassmann, Mario Gagov, Hristo Mladenov, Mitko Gollasch, Maik Schubert, Rudolf J Am Heart Assoc Original Research BACKGROUND: Multiple studies have shown that an NO‐induced activation of vascular smooth muscle BK channels contributes to the NO‐evoked dilation in many blood vessels. In vivo, NO is released continuously. NO attenuates vessel constrictions and, therefore, exerts an anticontractile effect. It is unknown whether the anticontractile effect of continuously present NO is mediated by BK channels. METHODS AND RESULTS: This study tested the hypothesis that BK channels mediate the vasodilatory effect of continuously present NO. Experiments were performed on rat and mouse tail and rat saphenous arteries using isometric myography and FURA‐2 fluorimetry. Continuously present NO donors, as well as endogenous NO, attenuated methoxamine‐induced vasoconstrictions. This effect was augmented in the presence of the BK channel blocker iberiotoxin. Moreover, the contractile effect of iberiotoxin was reduced in the presence of NO donors. The effect of the NO donor sodium nitroprusside was abolished by an NO scavenger and by a guanylyl cyclase inhibitor. In addition, the effect of sodium nitroprusside was reduced considerably by a protein kinase G inhibitor, but was not altered by inhibition of H(2)S generation. Sodium nitroprusside attenuated the intracellular calcium concentration response to methoxamine. Furthermore, sodium nitroprusside strongly reduced methoxamine‐induced calcium influx, which depends entirely on L‐type calcium channels. It did not affect methoxamine‐induced calcium release. CONCLUSIONS: In summary, this study demonstrates the following: (1) continuously present NO evokes a strong anticontractile effect on rat and mouse arteries; (2) the iberiotoxin‐induced augmentation of the effect of NO is associated with an NO‐induced reduction of the effect of iberiotoxin; and (3) NO evoked a reduction of calcium influx via L‐type calcium channels. John Wiley and Sons Inc. 2018-03-24 /pmc/articles/PMC5907584/ /pubmed/29574460 http://dx.doi.org/10.1161/JAHA.117.007808 Text en © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Research Schmid, Johannes Müller, Bettina Heppeler, David Gaynullina, Dina Kassmann, Mario Gagov, Hristo Mladenov, Mitko Gollasch, Maik Schubert, Rudolf The Unexpected Role of Calcium‐Activated Potassium Channels: Limitation of NO‐Induced Arterial Relaxation |
title | The Unexpected Role of Calcium‐Activated Potassium Channels: Limitation of NO‐Induced Arterial Relaxation |
title_full | The Unexpected Role of Calcium‐Activated Potassium Channels: Limitation of NO‐Induced Arterial Relaxation |
title_fullStr | The Unexpected Role of Calcium‐Activated Potassium Channels: Limitation of NO‐Induced Arterial Relaxation |
title_full_unstemmed | The Unexpected Role of Calcium‐Activated Potassium Channels: Limitation of NO‐Induced Arterial Relaxation |
title_short | The Unexpected Role of Calcium‐Activated Potassium Channels: Limitation of NO‐Induced Arterial Relaxation |
title_sort | unexpected role of calcium‐activated potassium channels: limitation of no‐induced arterial relaxation |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907584/ https://www.ncbi.nlm.nih.gov/pubmed/29574460 http://dx.doi.org/10.1161/JAHA.117.007808 |
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