Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
3224083
Reference Type
Journal Article
Title
The vasodilatory effect of sulfur dioxide via sGC/cGMP/PKG pathway in association with sulfhydryl-dependent dimerization
Author(s)
Yao, Q; Huang, Y; Liu, AD; Zhu, M; Liu, J; Yan, H; Zhang, Q; Geng, B; Gao, Y; Du, S; Huang, P; Tang, C; Du, J; Jin, H
Year
2016
Is Peer Reviewed?
Yes
Journal
American Journal of Physiology: Regulatory, Integrative and Comparative Physiology
ISSN:
0363-6119
EISSN:
1522-1490
Volume
310
Issue
11
Page Numbers
ajpregu.00101.2015
Language
English
PMID
27009048
DOI
10.1152/ajpregu.00101.2015
Web of Science Id
WOS:000377021700007
Abstract
The present study was designed to explore the role of soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway in sulfur dioxide (SO2)-induced vasodilation. We showed that SO2induced a concentration-dependent relaxation of phenylephrine (PE)-precontracted rat aortic rings in association with an increase in cGMP concentration, whereas L-aspartic acid β-hydroxamate (HDX), an inhibitor of SO2synthase, contracted rings in a dose-dependent manner. Pretreatment of aortic rings with the sGC inhibitor ODQ (30 μM) attenuated the vasodilatory effects of SO2, suggesting the involvement of cGMP pathway in SO2-induced vasodilation. Mechanistically, SO2upregulated the protein levels of sGC and PKG dimers, while HDX inhibited it, indicating SO2could promote cGMP synthesis through sGC activation. Furthermore, the dimerization of sGC and PKG and vasodilation induced by SO2in precontracted rings were significantly prevented by thiol reductants dithiothreitol (DTT). In addition, SO2reduced the activity of phosphodiesterase type 5 (PDE5), a cGMP-specific hydrolytic enzyme, implying that SO2elevated cGMP concentration by inhibiting its hydrolysis. Hence, SO2exerted its vasodilatory effects at least partly by promoting disulfide-dependent dimerization of sGC and PKG, resulting in an activated sGC/cGMP/PKG pathway in blood vessels. These findings revealed a new mode of action and mechanisms by which SO2regulated the vascular tone.
Keywords
dioxide; vasodilation; SGC; cGMP; PKG; dimer
Tags
NAAQS
•
ISA-SOx
Health Effects
Considered
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity