Open Access“A Step and a Ceiling”: mechanical properties of Ca 2+ spark vasoregulation in resistance arteries by pressure‐induced oxidative activation of PKG
Author(s) -
Csato Viktoria,
Kadir Sharifah Z. S. A.,
Khavandi Kaivan,
Bennett Hayley,
Sugden Sarah,
Gurney Alison M.,
Pritchard Harry A. T.,
HillEubanks David,
Eaton Philip,
Nelson Mark T.,
Greenstein Adam S.
Publication year - 2019
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.14260
Subject(s) - mesenteric arteries , electrical impedance myography , chemistry , vasodilation , oxidative phosphorylation , biophysics , artery , materials science , anatomy , medicine , biology , biochemistry
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.