Reactive oxygen species facilitate the EDH response in arterioles by potentiating intracellular endothelial Ca2+ release

Autor: Chidgey, James, Fraser, Paul A., Aaronson, Philip I.
Rok vydání: 2016
Předmět:
Male
H2O2
PGI2
prostacyclin
L-NNA
Nω-Nitro-l-arginine
IP3R
IP3 receptor
arteriole
Biochemistry
VSMC
vascular smooth muscle cell
IBTx
Iberiotoxin
Membrane Potentials
Biological Factors
AACOCF3
arachidonyl trifluoromethyl ketone
EDHR
EDH response
IL-1⍰
interleukin-1β
Arteriole
vasodilation
CPA
Cyclopiazonic Acid
reactive oxygen species
EDH
endothelial dependent hyperpolarization
Endothelium dependent hyperpolarization
cPLA2
cytoplasmic PLA2
Vasodilation
CP85
Na-1-ethylsulfoxide-2-methyl-3-hyroxypyridin-4-one
Arterioles
Ca2+
ODYA
17-octadecynoic acid
S&C
SOD and catalase
sEH
epoxide hydrolase
EDHF
EDH factor
Muscarinic Agonists
PPOH
2-(2-propynyloxy)-benzenehexanoic acid
Article
DFO
Desferrioxamine
PLC
phospholipase C
ROS
reactive oxygen species
SOD
superoxide dismutase
Physiology (medical)
Animals
Calcium Signaling
Rats
Wistar
NO
nitric oxide
EETs
epoxyeicosatrienoic acids
EEZE
4
15-epoxyeicosa-5(Z)-enoic acid
PE
phenylephrine
EC
endothelial cell
PSS
physiological salt solution
PLA2
phospholipase A2
CP94
1
2-diethyl-3-hyroxypyridin-4-one
HEPES
4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
Hydrogen Peroxide
AUDA
12-(3-adamantan-1-yl-ureido)dodecanoic acid
PKG
protein kinase G
Carbachol
EGTA
ethylene glycol-bis(β-aminoethyl ether)-N
N
N′
N′-tetraacetic acid
Endothelium
Vascular
Reactive oxygen species
L-NAME
N(G)-nitro-l-arginine methyl ester
SERCA
sarcoplasmic reticulum Ca2+-ATPase
Zdroj: Chidgey, J, Fraser, P A & Aaronson, P I 2016, ' Reactive oxygen species facilitate the EDH response in arterioles by potentiating intracellular endothelial Ca2+ release ', Free Radical Biology and Medicine . https://doi.org/10.1016/j.freeradbiomed.2016.06.010
Free Radical Biology & Medicine
ISSN: 0891-5849
DOI: 10.1016/j.freeradbiomed.2016.06.010
Popis: There is abundant evidence that H2O2 can act as an endothelium-derived hyperpolarizing factor in the resistance vasculature. However, whilst scavenging H2O2 can abolish endothelial dependent hyperpolarization (EDH) and the associated vascular relaxation in some arteries, EDH-dependent vasorelaxation can often be mimicked only by using relatively high concentrations of H2O2. We have examined the role of H2O2 in EDH-dependent vasodilatation by simultaneously measuring vascular diameter and changes in endothelial cell (EC) [Ca2+]i during the application of H2O2 or carbachol, which triggers EDH. Carbachol (10 µM) induced dilatation of phenylephrine-preconstricted rat cremaster arterioles was largely (73%) preserved in the presence of indomethacin (3 µM) and l-NAME (300 µM). This residual NO- and prostacyclin-independent dilatation was reduced by 89% upon addition of apamin (0.5 µM) and TRAM-34 (10 µM), and by 74% when an extracellular ROS scavenging mixture of SOD and catalase (S&C; 100 U ml−1 each) was present. S&C also reduced the carbachol-induced EC [Ca2+]i increase by 74%. When applied in Ca2+-free external medium, carbachol caused a transient increase in EC [Ca2+]i. This was reduced by catalase, and was enhanced when 1 µM H2O2 was present in the bath. H2O2 -induced dilatation, which occurred only at concentrations ≥100 µM, was reduced by a blocking antibody to TRPM2, which had no effect on carbachol-induced responses. Similarly, iberotoxin and Rp-8bromo cGMP reduced the vasodilatation induced by H2O2, but not by carbachol. Inhibiting PLC, PLA2 or CYP450 2C9 each greatly reduced the carbachol-induced increase in EC [Ca2+]i and vasodilatation, but adding 10 µM H2O2 during PLA2 or CYP450 2C9 inhibition completely restored both responses. The nature of the effective ROS species was investigated by using Fe2+ chelators to block the formation of ∙OH. A cell permeant chelator was able to inhibit EC Ca2+ store release, but cell impermeant chelators reduced both the vasodilatation and EC Ca2+ influx, implying that ∙OH is required for these responses. The results indicate that rather than mediating EDH by acting directly on smooth muscle, H2O2 promotes EDH by acting within EC to enhance Ca2+ release.
Graphical abstract fx1
Highlights • We recorded carbachol- evoked endothelial cell (EC) [Ca2+]i rises in rat arterioles. • Ca2+ rises were reduced by catalase, cPLA2 and CYP29C blockers, and iron chelators. • EC Ca2+ release was potentiated by 30 pM IL-1β or 1 μM exogenous H2O2. • H2O2 and carbachol evoked vasodilation, but by dissimilar mechanisms. • H2O2 promotes hyperpolarization-dependent dilatation by increasing EC Ca2+ release.
Databáze: OpenAIRE
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