Cargando…

“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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
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
_version_ 1783474302580948992
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
work_keys_str_mv AT csatoviktoria astepandaceilingmechanicalpropertiesofca2sparkvasoregulationinresistancearteriesbypressureinducedoxidativeactivationofpkg
AT kadirsharifahzsa astepandaceilingmechanicalpropertiesofca2sparkvasoregulationinresistancearteriesbypressureinducedoxidativeactivationofpkg
AT khavandikaivan astepandaceilingmechanicalpropertiesofca2sparkvasoregulationinresistancearteriesbypressureinducedoxidativeactivationofpkg
AT bennetthayley astepandaceilingmechanicalpropertiesofca2sparkvasoregulationinresistancearteriesbypressureinducedoxidativeactivationofpkg
AT sugdensarah astepandaceilingmechanicalpropertiesofca2sparkvasoregulationinresistancearteriesbypressureinducedoxidativeactivationofpkg
AT gurneyalisonm astepandaceilingmechanicalpropertiesofca2sparkvasoregulationinresistancearteriesbypressureinducedoxidativeactivationofpkg
AT pritchardharryt astepandaceilingmechanicalpropertiesofca2sparkvasoregulationinresistancearteriesbypressureinducedoxidativeactivationofpkg
AT hilleubanksdavid astepandaceilingmechanicalpropertiesofca2sparkvasoregulationinresistancearteriesbypressureinducedoxidativeactivationofpkg
AT eatonphilip astepandaceilingmechanicalpropertiesofca2sparkvasoregulationinresistancearteriesbypressureinducedoxidativeactivationofpkg
AT nelsonmarkt astepandaceilingmechanicalpropertiesofca2sparkvasoregulationinresistancearteriesbypressureinducedoxidativeactivationofpkg
AT greensteinadams astepandaceilingmechanicalpropertiesofca2sparkvasoregulationinresistancearteriesbypressureinducedoxidativeactivationofpkg