‘A Step and a Ceiling’Citation formats

  • External authors:
  • Viktoria Csato
  • Sharifah Z. Syed Abdul Kadir
  • Kaivan Khavandi
  • Hayley Bennett
  • David Hill-Eubanks
  • Philip Eaton

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‘A Step and a Ceiling’ : Mechanical properties of Ca2+ spark vasoregulation in resistance arteries by pressure-induced oxidative activation of PKG. / Csato, Viktoria; Syed Abdul Kadir, Sharifah Z.; Khavandi, Kaivan; Bennett, Hayley; Sugden, Sarah; Gurney, Alison; Pritchard, Harry; Hill-Eubanks, David ; Eaton, Philip ; Nelson, Mark; Greenstein, Adam.

In: Physiological Reports, Vol. 7, No. 22, e14260, 2020, p. 1-12.

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Author

Csato, Viktoria ; Syed Abdul Kadir, Sharifah Z. ; Khavandi, Kaivan ; Bennett, Hayley ; Sugden, Sarah ; Gurney, Alison ; Pritchard, Harry ; Hill-Eubanks, David ; Eaton, Philip ; Nelson, Mark ; Greenstein, Adam. / ‘A Step and a Ceiling’ : Mechanical properties of Ca2+ spark vasoregulation in resistance arteries by pressure-induced oxidative activation of PKG. In: Physiological Reports. 2020 ; Vol. 7, No. 22. pp. 1-12.

Bibtex

@article{f8cb0b4615cc4957ad49ef4507835363,
title = "{\textquoteleft}A Step and a Ceiling{\textquoteright}: Mechanical properties of Ca2+ spark vasoregulation in resistance arteries by pressure-induced oxidative activation of PKG",
abstract = "We investigated the biomechanical relationship between intraluminal pressure within small mesenteric resistance arteries, oxidant activation of PKG, Ca2+ 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. Ca2+ sparks and Ca2+ 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 Ca2+ sparks and also a functional “ceiling” for this pressure –‐sensitive oxidative pathway. During steady state pressure ‐ induced constriction, any additional Ca2+ 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 Ca2+ transient in pressurized arteries from mice with oxidant‐resistant PKG compared with wild type. Overall, we surmise that intraluminal pressure within resistance arteries controls Ca2+ 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 Ca2+ spark vasoregulation confer stability for the artery in order to provide a constant flow independent of additional pressure fluctuations or exogenous oxidants.",
keywords = "Ca2+ spark, vascular smooth muscle, oxygen signalling, Protein Kinase G, Pressure - induced constriction",
author = "Viktoria Csato and {Syed Abdul Kadir}, {Sharifah Z.} and Kaivan Khavandi and Hayley Bennett and Sarah Sugden and Alison Gurney and Harry Pritchard and David Hill-Eubanks and Philip Eaton and Mark Nelson and Adam Greenstein",
year = "2020",
doi = "10.14814/phy2.14260",
language = "English",
volume = "7",
pages = "1--12",
journal = "Physiological Reports",
publisher = "John Wiley & Sons Ltd",
number = "22",

}

RIS

TY - JOUR

T1 - ‘A Step and a Ceiling’

T2 - Mechanical properties of Ca2+ spark vasoregulation in resistance arteries by pressure-induced oxidative activation of PKG

AU - Csato, Viktoria

AU - Syed Abdul Kadir, Sharifah Z.

AU - Khavandi, Kaivan

AU - Bennett, Hayley

AU - Sugden, Sarah

AU - Gurney, Alison

AU - Pritchard, Harry

AU - Hill-Eubanks, David

AU - Eaton, Philip

AU - Nelson, Mark

AU - Greenstein, Adam

PY - 2020

Y1 - 2020

N2 - We investigated the biomechanical relationship between intraluminal pressure within small mesenteric resistance arteries, oxidant activation of PKG, Ca2+ 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. Ca2+ sparks and Ca2+ 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 Ca2+ sparks and also a functional “ceiling” for this pressure –‐sensitive oxidative pathway. During steady state pressure ‐ induced constriction, any additional Ca2+ 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 Ca2+ transient in pressurized arteries from mice with oxidant‐resistant PKG compared with wild type. Overall, we surmise that intraluminal pressure within resistance arteries controls Ca2+ 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 Ca2+ spark vasoregulation confer stability for the artery in order to provide a constant flow independent of additional pressure fluctuations or exogenous oxidants.

AB - We investigated the biomechanical relationship between intraluminal pressure within small mesenteric resistance arteries, oxidant activation of PKG, Ca2+ 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. Ca2+ sparks and Ca2+ 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 Ca2+ sparks and also a functional “ceiling” for this pressure –‐sensitive oxidative pathway. During steady state pressure ‐ induced constriction, any additional Ca2+ 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 Ca2+ transient in pressurized arteries from mice with oxidant‐resistant PKG compared with wild type. Overall, we surmise that intraluminal pressure within resistance arteries controls Ca2+ 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 Ca2+ spark vasoregulation confer stability for the artery in order to provide a constant flow independent of additional pressure fluctuations or exogenous oxidants.

KW - Ca2+ spark

KW - vascular smooth muscle

KW - oxygen signalling

KW - Protein Kinase G

KW - Pressure - induced constriction

U2 - 10.14814/phy2.14260

DO - 10.14814/phy2.14260

M3 - Article

VL - 7

SP - 1

EP - 12

JO - Physiological Reports

JF - Physiological Reports

IS - 22

M1 - e14260

ER -