Protein kinase C delta modulates endothelial nitric oxide synthase after cardiac arrest

Hung Wen Lin, Victoria L. Gresia, Holly M. Stradecki, Aleksey Alekseyenko, Cameron Dezfulian, Jake T. Neumann, Kunjan R. Dave, Miguel A. Perez-Pinzon

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

We previously showed that inhibition of protein kinase C delta (PKCδ) improves brain perfusion 24 hours after asphyxial cardiac arrest (ACA) and confers neuroprotection in the cortex and CA1 region of the hippocampus 7 days after arrest. Therefore, in this study, we investigate the mechanism of action of PKCδ-mediated hypoperfusion after ACA in the rat by using the two-photon laser scanning microscopy (TPLSM) to observe cortical cerebral blood flow (CBF) and laser Doppler flowmetry (LDF) detecting regional CBF in the presence/absence of δV1-1 (specific PKCδ inhibitor), nitric oxide synthase (NOS) substrate (L-arginine, L-arg) and inhibitor (Nω -Nitro-L-arginine, NLA), and nitric oxide (NO) donor (sodium nitroprusside, SNP). There was an increase in regional LDF and local (TPLSM) CBF in the presence of δV1-1+L-arg, but only an increase in regional CBF under δV1-1+SNP treatments. Systemic blood nitrite levels were measured 15 minutes and 24 hours after ACA. Nitrite levels were enhanced by pretreatment with δV1-1 30 minutes before ACA possibly attributable to enhanced endothelial NOS protein levels. Our results suggest that PKCδ can modulate NO machinery in cerebral vasculature. Protein kinase C delta can depress endothelial NOS blunting CBF resulting in hypoperfusion, but can be reversed with δV1-1 improving brain perfusion, thus providing subsequent neuroprotection after ACA.

Original languageEnglish (US)
Pages (from-to)613-620
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume34
Issue number4
DOIs
StatePublished - Apr 2014

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Keywords

  • Asphyxial cardiac arrest
  • Middle cerebral artery occlusion
  • Neuroprotection
  • Palmitic acid methyl ester
  • Stearic acid methyl ester

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

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