The role of ATP sensitive K+ channels and of nitric oxide synthase on myocardial ischemia/reperfusion-induced apoptosis

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dc.contributor.authorGok S.
dc.contributor.authorVatansever S.
dc.contributor.authorVural K.
dc.contributor.authorSekuri C.
dc.contributor.authorIzanli A.
dc.contributor.authorTezcan A.
dc.contributor.authorCilaker S.
dc.date.accessioned2024-07-22T08:23:30Z
dc.date.available2024-07-22T08:23:30Z
dc.date.issued2006
dc.description.abstractDuring ischemia, ATP-sensitive K+ channels (KATP channels) open, and this triggers necrotic processes and apoptosis. In this study, we investigated whether selective sarcoplasmic and mitochondrial KATP channel blockers affected myocardial apoptosis and nitric oxide synthase (NOS) activity in a rat model of myocardial ischemia/reperfusion in vitro. Isolated rat hearts were subjected to 30 min of coronary artery occlusion followed by 30 min of reperfusion. A selective sarcKATP channel blocker, HMR1098 and a selective mitoKATP channel blocker, 5-hydroxydecanoate, were added to the perfusion fluid 10 min before occlusion. Myocardial apoptosis was detected immunohistochemically using the TUNEL method. Myocardial inducible NOS (iNOS) and endothelial NOS (eNOS) were determined immunohistochemically. In control hearts, apoptosis induction was associated with a greater immunoreactivity of iNOS than eNOS. Treatment with HMR1098, at a concentration of 3 μmol/l, significantly reduced the TUNEL-positive cardiomyocytes and this was associated with decreased iNOS and increased eNOS immunoreactivity. When this drug was administered at a higher concentration, at 30 μmol/l, a more marked reduction in apoptosis was observed but, in contrast to the effects observed at the lower drug concentration, eNOS immunoreactivity was almost completely abolished while iNOS was strong. Moreover, ischemia-induced cardiac dysfunction (e.g. contractile force and recovery of coronary flow) was increased by the higher concentration of HMR 1098. In hearts treated with 5-hydroxydecanoate, myocyte apoptosis was slightly reduced, and this was associated with an almost equal increase in both iNOS and eNOS immunoreactivity. These findings suggest that iNOS appears to be more important than eNOS in the reduction of apoptosis. However, the further inhibition of apoptosis by the higher concentration of HMR 1098 was associated with poorer cardiac function. © 2006 Elsevier GmbH. All rights reserved.
dc.identifier.DOI-ID10.1016/j.acthis.2006.01.005
dc.identifier.issn00651281
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/19568
dc.language.isoEnglish
dc.publisherElsevier GmbH
dc.subjectDrug dosage
dc.subjectEnzyme inhibition
dc.subjectEnzyme kinetics
dc.subjectImmunology
dc.subjectMathematical models
dc.subjectNitrogen oxides
dc.subject5 hydroxydecanoic acid
dc.subjectadenosine triphosphate sensitive potassium channel
dc.subjectclamikalant
dc.subjectendothelial nitric oxide synthase
dc.subjectinducible nitric oxide synthase
dc.subjectnitric oxide synthase
dc.subjectApoptosis
dc.subjectIschemia-reperfusion
dc.subjectIsolated rat heart
dc.subjectNitric oxide
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectapoptosis
dc.subjectarticle
dc.subjectcontrolled study
dc.subjectcoronary artery blood flow
dc.subjectenzyme activity
dc.subjectenzyme induction
dc.subjectheart disease
dc.subjectheart function
dc.subjectheart infarction
dc.subjectheart mitochondrion
dc.subjectheart muscle cell
dc.subjectheart muscle contractile force
dc.subjectheart muscle ischemia
dc.subjectheart muscle perfusion
dc.subjectheart muscle reperfusion
dc.subjectimmunohistochemistry
dc.subjectimmunoreactivity
dc.subjectisolated heart
dc.subjectnick end labeling
dc.subjectnonhuman
dc.subjectrat
dc.subjectreperfusion injury
dc.subjectsarcoplasmic reticulum
dc.subjectAdenosinetriphosphate
dc.titleThe role of ATP sensitive K+ channels and of nitric oxide synthase on myocardial ischemia/reperfusion-induced apoptosis
dc.typeArticle

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