OBJECTIVE: Hydrogen peroxide (H(2)O(2)) is an important mediator in the 
vasculature, but its role in the regulation of soluble guanylate cyclase (sGC) 
activity and expression is not completely understood. The aim of this study was 
to test the effect of H(2)O(2) on sGC expression and function and to explore the 
molecular mechanism involved.
METHODS AND RESULTS: H(2)O(2) increased sGCβ1 protein steady-state levels in rat 
aorta and aortic smooth muscle cells (RASMCs) in a time- and dose-dependent 
manner, and this effect was blocked by catalase. sGCα2 expression increased 
along with β1 subunit, whereas α1 subunit remained unchanged. Vascular 
relaxation to an NO donor (sodium nitroprusside) was enhanced by H(2)O(2), and 
it was prevented by ODQ (sGC inhibitor). cGMP production in both freshly 
isolated vessels and RASMCs exposed to H(2)O(2) was greatly increased after 
sodium nitroprusside treatment. The H(2)O(2)-dependent sGCβ1 upregulation was 
attributable to sGCβ1 mRNA stabilization, conditioned by the translocation of 
the mRNA-binding protein HuR from the nucleus to the cytosol, and the increased 
mRNA binding of HuR to the sGCβ1 3' untranslated region. HuR silencing reversed 
the effects of H(2)O(2) on sGCβ1 levels and cGMP synthesis.
CONCLUSIONS: Our results identify H(2)O(2) as an endogenous mediator 
contributing to the regulation of vascular tone and point to a key role of HuR 
in sGCβ1 mRNA stabilization.