In:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 310, No. 11 ( 2016-06-01), p. R1073-R1080
Abstract:
The present study was designed to explore the role of soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/PKG pathway in sulfur dioxide (SO 2 )-induced vasodilation. We showed that SO 2 induced 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 SO 2 synthase, contracted rings in a dose-dependent manner. Pretreatment of aortic rings with the sGC inhibitor ODQ (30 μM) attenuated the vasodilatory effects of SO 2 , suggesting the involvement of cGMP pathway in SO 2 -induced vasodilation. Mechanistically, SO 2 upregulated the protein levels of sGC and PKG dimers, while HDX inhibited it, indicating SO 2 could promote cGMP synthesis through sGC activation. Furthermore, the dimerization of sGC and PKG and vasodilation induced by SO 2 in precontracted rings were significantly prevented by thiol reductants dithiothreitol (DTT). In addition, SO 2 reduced the activity of phosphodiesterase type 5 (PDE5), a cGMP-specific hydrolytic enzyme, implying that SO 2 elevated cGMP concentration by inhibiting its hydrolysis. Hence, SO 2 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 SO 2 regulated the vascular tone.
Type of Medium:
Online Resource
ISSN:
0363-6119
,
1522-1490
DOI:
10.1152/ajpregu.00101.2015
Language:
English
Publisher:
American Physiological Society
Publication Date:
2016
detail.hit.zdb_id:
603839-6
detail.hit.zdb_id:
1477297-8
SSG:
12
