Reperfusion damage involves opening of the
mitochondrial permeability transition pore (mPTP) and loss of
ATP synthesis. Several cardioprotective pathways are activated by ischemic or pharmacological post-conditioning (PC). The mechanisms that are activated by PC in no co-morbidity murine models include: activation of rescue
kinases, oxidative stress reduction, glycolytic flux regulation and preservation of
ATP synthesis. However, relatively scarce efforts have been made to define whether the efficacy of PC signaling is blunted by risk factors or systemic diseases associated with ischemic heart pathology. Experimental evidence has shown that the
nitric oxide (NO)/cyclic
guanosine monophosphate (cGMP) signaling is a main mechanism activated by PC in hearts without pathological history. In this work we evaluated the participation of the NO pathway, through downstream
kinase activation and inhibition of
mPTP in hearts with previous
infarct.
Myocardial infarction was induced with a single dose of
isoproterenol (85 mg/kg i.p.) to male Wistar rats. After 24 h, the hearts were mounted into the Langendorff system and subjected to 30 min of
ischemia and 60 min of reperfusion. PC consisted of 5 cycles of 30 s of reperfusion/30 s of
ischemia, then the hearts were reperfused with or without inhibitors of the NO/cGMP pathway. PC activates the NO/cGMP pathway, as increased cGMP and NO levels were detected in
isoproterenol-treated hearts. The cardioprotective effect of PC was abolished with both
L-NAME (inhibitor of constitutive
NO synthase) and ODQ (inhibitor of
soluble guanylate cyclase), whereas the NO donor (
DETA-NO) restored cardioprotection even in the presence of
L-NAME or ODQ. We also found that mitochondrial structure and function was preserved in PC hearts. We conclude that PC exerts cardioprotection in hearts with previous
infarct by maintaining mitochondrial structure and function through NO-dependent pathway.