PMID- 29550336
OWN - NLM
STAT- MEDLINE
DCOM- 20181009
LR  - 20181009
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 827
DP  - 2018 May 15
TI  - Endothelium-derived hyperpolarizing factor and protein kinase G Ialpha activation: 
      H(2)O(2) versus S-nitrosothiols.
PG  - 112-116
LID - S0014-2999(18)30173-0 [pii]
LID - 10.1016/j.ejphar.2018.03.019 [doi]
AB  - Protein kinase G (PKG) Ialpha mediates the cyclic guanosine monophosphate-mediated 
      vasodilatory effects induced by NO. Endothelium-derived hyperpolarizing factors 
      (EDHFs), like H(2)O(2) can activate PKGIalpha in a cyclic guanosine 
      monophosphate-independent manner, but whether this is true for all EDHFs (e.g., 
      S-nitrosothiols) is unknown. Here, we investigated the contribution of PKGIalpha to 
      bradykinin-, H(2)O(2)-, L-S-nitrosocysteine-, and light-induced relaxation in 
      porcine coronary arteries, making use of the fact that thioredoxin reductase 
      inhibition with auranofin or 1-chloro-2,4-dinitrobenzene potentiates PKGIalpha. 
      Thioredoxin reductase inhibition potentiated bradykinin and H(2)O(2), but not 
      L-S-nitrosocysteine or light. The relaxations by the latter 2 and bradykinin, but 
      not those by H(2)O(2), were prevented by the soluble guanylyl cyclase (sGC) 
      inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Yet, after S-nitrosothiol 
      depletion with ethacrynic acid, thioredoxin reductase inhibition also potentiated 
      light-induced relaxation, and this was prevented by the Na(+)-K(+) ATPase 
      inhibitor ouabain. This indicates that photorelaxation depends on sGC activation 
      by S-nitrosothiols, while only after S-nitrosothiol depletion oxidized PKGIalpha 
      comes into play, and acts via Na(+)-K(+) ATPase. In conclusion, both bradykinin- 
      and light-induced relaxation of porcine coronary arteries depend, at least 
      partially, on oxidized PKGIalpha, and this does not involve sGC. H(2)O(2) also acts 
      via oxidized PKGIalpha in an sGC-independent manner. Yet, S-nitrosothiol-induced 
      relaxation is PKGIalpha-independent. Clearly, PKG activation does not contribute 
      universally to all EDHF responses, and targeting PKGIalpha may only mimick EDHF under 
      certain conditions. It is therefore unlikely that PKGIalpha activators will be 
      universal vasodilators.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Bautista-Nino, Paula K
AU  - Bautista-Nino PK
AD  - Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, 
      Erasmus Medical Center, Rotterdam, The Netherlands.
FAU - van der Stel, Marien
AU  - van der Stel M
AD  - Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, 
      Erasmus Medical Center, Rotterdam, The Netherlands.
FAU - Batenburg, Wendy W
AU  - Batenburg WW
AD  - Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, 
      Erasmus Medical Center, Rotterdam, The Netherlands.
FAU - de Vries, Rene
AU  - de Vries R
AD  - Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, 
      Erasmus Medical Center, Rotterdam, The Netherlands.
FAU - Roks, Anton J M
AU  - Roks AJM
AD  - Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, 
      Erasmus Medical Center, Rotterdam, The Netherlands.
FAU - Danser, A H Jan
AU  - Danser AHJ
AD  - Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, 
      Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: 
      a.danser@erasmusmc.nl.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20180314
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Biological Factors)
RN  - 0 (S-Nitrosothiols)
RN  - 0 (endothelium-dependent hyperpolarization factor)
RN  - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinase Type I)
SB  - IM
MH  - Animals
MH  - Biological Factors/*metabolism
MH  - Cyclic GMP-Dependent Protein Kinase Type I/*metabolism
MH  - Enzyme Activation/drug effects
MH  - S-Nitrosothiols/*pharmacology
MH  - Swine
OTO - NOTNLM
OT  - Endothelium-derived hyperpolarizing factors
OT  - Protein kinase G Ialpha
OT  - S-nitrosothiols
OT  - Soluble guanylyl cyclase
OT  - Thioredoxin reductase
EDAT- 2018/03/20 06:00
MHDA- 2018/10/10 06:00
CRDT- 2018/03/19 06:00
PHST- 2017/10/06 00:00 [received]
PHST- 2018/03/08 00:00 [revised]
PHST- 2018/03/13 00:00 [accepted]
PHST- 2018/03/20 06:00 [pubmed]
PHST- 2018/10/10 06:00 [medline]
PHST- 2018/03/19 06:00 [entrez]
AID - S0014-2999(18)30173-0 [pii]
AID - 10.1016/j.ejphar.2018.03.019 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2018 May 15;827:112-116. doi: 10.1016/j.ejphar.2018.03.019. Epub 
      2018 Mar 14.