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 Perez-Pinzon

Research output: Contribution to journalArticle

10 Citations (Scopus)

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
Pages (from-to)613-620
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume34
Issue number4
DOIs
StatePublished - Jan 1 2014

Fingerprint

Cerebrovascular Circulation
Protein Kinase C-delta
Nitric Oxide Synthase Type III
Heart Arrest
Laser-Doppler Flowmetry
Regional Blood Flow
Nitroprusside
Nitrites
Photons
Confocal Microscopy
Arginine
Perfusion
Nitric Oxide Donors
Brain
Nitric Oxide Synthase
Hippocampus
Nitric Oxide

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

Cite this

Protein kinase C delta modulates endothelial nitric oxide synthase after cardiac arrest. / Wen Lin, Hung; Gresia, Victoria L.; Stradecki, Holly M.; Alekseyenko, Aleksey; Dezfulian, Cameron; Neumann, Jake T.; Dave, Kunjan R; Perez-Pinzon, Miguel.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 34, No. 4, 01.01.2014, p. 613-620.

Research output: Contribution to journalArticle

Wen Lin, Hung ; Gresia, Victoria L. ; Stradecki, Holly M. ; Alekseyenko, Aleksey ; Dezfulian, Cameron ; Neumann, Jake T. ; Dave, Kunjan R ; Perez-Pinzon, Miguel. / Protein kinase C delta modulates endothelial nitric oxide synthase after cardiac arrest. In: Journal of Cerebral Blood Flow and Metabolism. 2014 ; Vol. 34, No. 4. pp. 613-620.
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