The vasodilatory effect of sulfur dioxide via SGC/cGMP/PKG pathway in association with sulfhydryl-dependent dimerization
2016 (English)In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 310, no 11, R1073-R1080 p.Article in journal (Refereed) PublishedText
The present study was designed to explore the role of soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/PKG pathway in sulfur dioxide (SO2)-induced vasodilation. We showed that SO2 induced a concentration-dependent relaxation of phenylephrine (PE)precontracted rat aortic rings in association with an increase in cGMP concentration, whereas L-aspartic acid beta-hydroxamate (HDX), an inhibitor of SO2 synthase, contracted rings in a dose-dependent manner. Pretreatment of aortic rings with the sGC inhibitor ODQ (30 mu M) attenuated the vasodilatory effects of SO2, suggesting the involvement of cGMP pathway in SO2-induced vasodilation. Mechanistically, SO2 upregulated the protein levels of sGC and PKG dimers, while HDX inhibited it, indicating SO2 could promote cGMP synthesis through sGC activation. Furthermore, the dimerization of sGC and PKG and vasodilation induced by SO2 in precontracted rings were significantly prevented by thiol reductants dithiothreitol (DTT). In addition, SO2 reduced the activity of phosphodiesterase type 5 (PDE5), a cGMP-specific hydrolytic enzyme, implying that SO2 elevated cGMP concentration by inhibiting its hydrolysis. Hence, SO2 exerted 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 SO2 regulated the vascular tone.
Place, publisher, year, edition, pages
AMER PHYSIOLOGICAL SOC , 2016. Vol. 310, no 11, R1073-R1080 p.
dioxide; vasodilation; SGC; cGMP; PKG; dimer
IdentifiersURN: urn:nbn:se:liu:diva-129666DOI: 10.1152/ajpregu.00101.2015ISI: 000377021700007PubMedID: 27009048OAI: oai:DiVA.org:liu-129666DiVA: diva2:943195
Funding Agencies|National Natural Sciences Foundation of China [31130030, 81400311, 91439110]; Beijing National Nature Science Foundation ; National Youth Top-notch Talent Support Program, Major Basic Research Project of China [2012CB517806]2016-06-272016-06-232016-06-27