Several studies have demonstrated the role of endothelial and
inducible nitric oxide synthase in cardiac
ischemia reperfusion(IR). However, the role of
neuronal nitric oxide synthase (nNOS) in IR is still controversial. The present study was designed to explore the possible involvement of nNOS in cardiac IR. nNOS-/- knockout (KO) and wild type C57 (WT) mice were subjected to 45 min of
ischemia by left descending branch of coronary artery
ligation followed by 3 h reperfusion, which plasma was collected for
creatine kinase (CK) and
lactate dehydrogenase (LDH) measurements,
terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and measurements of activities of
caspase-3, -8, -9, phospho-p38, -ERK, -JNK
mitogen-activated protein kinase (MAPK) and phospho-nNOS, phospho-eNOS and iNOS. IR induced cardiac tissue apoptosis by increases of TUNEL staining and activities of
caspase-3, -8, and -9, accompanied with increase of CK and LDH concentration and phosphorylation of p38, ERK and JNK MAPK and phospho-nNOS, phospho-eNOS and iNOS in both mouse strains. However, IR induced increases of TUNEL staining and activities of
caspase-3, -8 and -9, and CK and LDH concentrations and activation of
p38 MAPK were markedly lower in KO mice compared with WT mice. But the phosphorylation of eNOS was significantly higher compared with WT IR group (P < 0.05). The data obtained suggest that nNOS exacerbates IR-induced injury maybe involving
p38 MAPK activation.