We are not able to resolve this OAI Identifier to the repository landing page. If you are the repository manager for this record, please head to the Dashboard and adjust the settings.
OBJECTIVE: Recent studies have demonstrated that hydrogen sulfide (H(2)S) is
produced within the vessel wall from L-cysteine regulating several aspects of
vascular homeostasis. H(2)S generated from cystathione γ-lyase (CSE) contributes
to vascular tone; however, the molecular mechanisms underlying the vasorelaxing
effects of H(2)S are still under investigation.
METHODS AND RESULTS: Using isolated aortic rings, we observed that addition of
L-cysteine led to a concentration-dependent relaxation that was prevented by the
CSE inhibitors DL-propargylglyicine (PAG) and β-cyano-l-alanine (BCA). Moreover,
incubation with PAG or BCA resulted in a rightward shift in sodium
nitroprusside-and isoproterenol-induced relaxation. Aortic tissues exposed to PAG
or BCA contained lower levels of cGMP, exposure of cells to exogenous H(2)S or
overexpression of CSE raised cGMP concentration. RNA silencing of CSE expression
reduced intracellular cGMP levels confirming a positive role for endogenous H(2)S
on cGMP accumulation. The ability of H(2)S to enhance cGMP levels was greatly
reduced by the nonselective phosphodiesterase inhibitor
3-isobutyl-1-methylxanthine. Finally, addition of H(2)S to a cell-free system
inhibited both cGMP and cAMP breakdown.
CONCLUSIONS: These findings provide direct evidence that H(2)S acts as an
endogenous inhibitor of phosphodiesterase activity and reinforce the notion that
this gasotransmitter could be therapeutically exploited
Is data on this page outdated, violates copyrights or anything else? Report the problem now and we will take corresponding actions after reviewing your request.