Document Detail


NO-independent stimulation or activation of soluble guanylyl cyclase during early reperfusion limits infarct size.
MedLine Citation:
PMID:  24253521     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Guanylyl cyclase - cyclic guanosine monophosphate signalling plays an important role in endogenous cardioprotective signalling. The aim was to assess the potential of direct pharmacological activation and stimulation of soluble guanylyl cyclase, targeting different redox states of the enzyme, to limit myocardial necrosis during early reperfusion.Methods and ResultsRat isolated hearts were subjected to reversible left coronary artery occlusion (ischemia-reperfusion) and infarct size was assessed by the tetrazolium staining technique. Administration during early reperfusion of BAY 41-2272, an NO-independent, haem-dependent stimulator of soluble guanylyl cyclase targeting the reduced state, or BAY 60-2770, an NO-independent, haem-independent activator targeting the oxidised state, significantly limited infarct size. Inhibition of NO synthesis did not abrogate this protection, but exogenous perfusion of NO with BAY 41-2272 produced a synergistic effect. The haem site oxidiser, ODQ abrogated the protection afforded by BAY 41-2272 but potentiated the protection afforded by BAY 60-2770. Targeting both the reduced and oxidised forms of sGC together did not afford additive protection.
CONCLUSIONS: Targeting either reduced or oxidised forms of sGC during early reperfusion affords cardioprotection, providing support for the concept that direct sGC manipulation at reperfusion has therapeutic potential for the management of acute myocardial infarction.
Authors:
Justin S Bice; Yvonne Keim; Johannes-Peter Stasch; Gary F Baxter
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-11-18
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, UK.
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