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 language | English |
|---|---|
| Pages (from-to) | 613-620 |
| Number of pages | 8 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 34 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jan 1 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
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 journal › Article
}
TY - JOUR
T1 - Protein kinase C delta modulates endothelial nitric oxide synthase after cardiac arrest
AU - Wen Lin, Hung
AU - Gresia, Victoria L.
AU - Stradecki, Holly M.
AU - Alekseyenko, Aleksey
AU - Dezfulian, Cameron
AU - Neumann, Jake T.
AU - Dave, Kunjan R
AU - Perez-Pinzon, Miguel
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Asphyxial cardiac arrest
KW - Middle cerebral artery occlusion
KW - Neuroprotection
KW - Palmitic acid methyl ester
KW - Stearic acid methyl ester
UR - http://www.scopus.com/inward/record.url?scp=84897574509&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897574509&partnerID=8YFLogxK
U2 - 10.1038/jcbfm.2013.232
DO - 10.1038/jcbfm.2013.232
M3 - Article
VL - 34
SP - 613
EP - 620
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 4
ER -