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“A Step and a Ceiling”: mechanical properties of Ca(2+) spark vasoregulation in resistance arteries by pressure‐induced oxidative activation of PKG
We investigated the biomechanical relationship between intraluminal pressure within small mesenteric resistance arteries, oxidant activation of PKG, Ca(2+) sparks, and BK channel vasoregulation. Mesenteric resistance arteries from wild type (WT) and genetically modified mice with PKG resistance to o...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883097/ https://www.ncbi.nlm.nih.gov/pubmed/31782255 http://dx.doi.org/10.14814/phy2.14260 |
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author | Csato, Viktoria Kadir, Sharifah Z. S. A. Khavandi, Kaivan Bennett, Hayley Sugden, Sarah Gurney, Alison M. Pritchard, Harry T. Hill‐Eubanks, David Eaton, Philip Nelson, Mark T. Greenstein, Adam S. |
author_facet | Csato, Viktoria Kadir, Sharifah Z. S. A. Khavandi, Kaivan Bennett, Hayley Sugden, Sarah Gurney, Alison M. Pritchard, Harry T. Hill‐Eubanks, David Eaton, Philip Nelson, Mark T. Greenstein, Adam S. |
author_sort | Csato, Viktoria |
collection | PubMed |
description | We investigated the biomechanical relationship between intraluminal pressure within small mesenteric resistance arteries, oxidant activation of PKG, Ca(2+) sparks, and BK channel vasoregulation. Mesenteric resistance arteries from wild type (WT) and genetically modified mice with PKG resistance to oxidative activation were studied using wire and pressure myography. Ca(2+) sparks and Ca(2+) transients within vascular smooth muscle cells of intact arteries were characterized using high‐speed confocal microscopy of intact arteries. Arteries were studied under conditions of varying intraluminal pressure and oxidation. Intraluminal pressure specifically, rather than the generic stretch of the artery, was necessary to activate the oxidative pathway. We demonstrated a graded step activation profile for the generation of Ca(2+) sparks and also a functional “ceiling” for this pressure –‐sensitive oxidative pathway. During steady state pressure ‐ induced constriction, any additional Ca(2+) sensitive‐K(+) channel functional availability was independent of oxidant activated PKG. There was an increase in the amplitude, but not the Area under the Curve (AUC) of the caffeine‐induced Ca(2+) transient in pressurized arteries from mice with oxidant‐resistant PKG compared with wild type. Overall, we surmise that intraluminal pressure within resistance arteries controls Ca(2+) spark vasoregulation through a tightly controlled pathway with a graded onset switch. The pathway, underpinned by oxidant activation of PKG, cannot be further boosted by additional pressure or oxidation once active. We propose that these restrictive characteristics of pressure‐induced Ca(2+) spark vasoregulation confer stability for the artery in order to provide a constant flow independent of additional pressure fluctuations or exogenous oxidants. |
format | Online Article Text |
id | pubmed-6883097 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68830972019-12-03 “A Step and a Ceiling”: mechanical properties of Ca(2+) spark vasoregulation in resistance arteries by pressure‐induced oxidative activation of PKG Csato, Viktoria Kadir, Sharifah Z. S. A. Khavandi, Kaivan Bennett, Hayley Sugden, Sarah Gurney, Alison M. Pritchard, Harry T. Hill‐Eubanks, David Eaton, Philip Nelson, Mark T. Greenstein, Adam S. Physiol Rep Original Research We investigated the biomechanical relationship between intraluminal pressure within small mesenteric resistance arteries, oxidant activation of PKG, Ca(2+) sparks, and BK channel vasoregulation. Mesenteric resistance arteries from wild type (WT) and genetically modified mice with PKG resistance to oxidative activation were studied using wire and pressure myography. Ca(2+) sparks and Ca(2+) transients within vascular smooth muscle cells of intact arteries were characterized using high‐speed confocal microscopy of intact arteries. Arteries were studied under conditions of varying intraluminal pressure and oxidation. Intraluminal pressure specifically, rather than the generic stretch of the artery, was necessary to activate the oxidative pathway. We demonstrated a graded step activation profile for the generation of Ca(2+) sparks and also a functional “ceiling” for this pressure –‐sensitive oxidative pathway. During steady state pressure ‐ induced constriction, any additional Ca(2+) sensitive‐K(+) channel functional availability was independent of oxidant activated PKG. There was an increase in the amplitude, but not the Area under the Curve (AUC) of the caffeine‐induced Ca(2+) transient in pressurized arteries from mice with oxidant‐resistant PKG compared with wild type. Overall, we surmise that intraluminal pressure within resistance arteries controls Ca(2+) spark vasoregulation through a tightly controlled pathway with a graded onset switch. The pathway, underpinned by oxidant activation of PKG, cannot be further boosted by additional pressure or oxidation once active. We propose that these restrictive characteristics of pressure‐induced Ca(2+) spark vasoregulation confer stability for the artery in order to provide a constant flow independent of additional pressure fluctuations or exogenous oxidants. John Wiley and Sons Inc. 2019-11-28 /pmc/articles/PMC6883097/ /pubmed/31782255 http://dx.doi.org/10.14814/phy2.14260 Text en © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Csato, Viktoria Kadir, Sharifah Z. S. A. Khavandi, Kaivan Bennett, Hayley Sugden, Sarah Gurney, Alison M. Pritchard, Harry T. Hill‐Eubanks, David Eaton, Philip Nelson, Mark T. Greenstein, Adam S. “A Step and a Ceiling”: mechanical properties of Ca(2+) spark vasoregulation in resistance arteries by pressure‐induced oxidative activation of PKG |
title | “A Step and a Ceiling”: mechanical properties of Ca(2+) spark vasoregulation in resistance arteries by pressure‐induced oxidative activation of PKG |
title_full | “A Step and a Ceiling”: mechanical properties of Ca(2+) spark vasoregulation in resistance arteries by pressure‐induced oxidative activation of PKG |
title_fullStr | “A Step and a Ceiling”: mechanical properties of Ca(2+) spark vasoregulation in resistance arteries by pressure‐induced oxidative activation of PKG |
title_full_unstemmed | “A Step and a Ceiling”: mechanical properties of Ca(2+) spark vasoregulation in resistance arteries by pressure‐induced oxidative activation of PKG |
title_short | “A Step and a Ceiling”: mechanical properties of Ca(2+) spark vasoregulation in resistance arteries by pressure‐induced oxidative activation of PKG |
title_sort | “a step and a ceiling”: mechanical properties of ca(2+) spark vasoregulation in resistance arteries by pressure‐induced oxidative activation of pkg |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883097/ https://www.ncbi.nlm.nih.gov/pubmed/31782255 http://dx.doi.org/10.14814/phy2.14260 |
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