PMID- 24336015
OWN - NLM
STAT- MEDLINE
DCOM- 20141228
LR  - 20211021
IS  - 1533-4023 (Electronic)
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 63
IP  - 5
DP  - 2014 May
TI  - Enhanced vascular PI3K/Akt-NOX signaling underlies the peripheral NMDAR-mediated 
      pressor response in conscious rats.
PG  - 395-405
LID - 10.1097/FJC.0000000000000059 [doi]
AB  - The molecular mechanisms for peripheral N-methyl-D-aspartate receptor 
      (NMDAR)-mediated vascular oxidative stress and pressor response are not known. We 
      conducted integrative (in vivo) and ex vivo biochemical studies to test the 
      hypothesis that reactive oxygen species (ROS)-dependent calcium influx, triggered 
      by the activation of vascular kinases, underlies the NMDAR-mediated pressor 
      response. Pharmacological inhibition of phosphoinositide 3-kinase (PI3K)/Akt 
      (wortmannin, 15 mug/kg), protein kinase C (chelerythrine: 5 mg/kg, intravenous), 
      Ca(2)(+) influx (nifedipine, 0.35 or 0.75 mg/kg), or NADPH oxidase (NOX: apocynin, 5 
      mg/kg) attenuated the peripheral NMDAR-mediated pressor response in conscious 
      male Sprague-Dawley rats. NMDAR activation enhanced the phosphorylation of Akt, 
      ERK1, JNK and p38 (Western blot), and NOX activity in vascular tissues collected 
      during the pressor response caused by NMDA infusion (180 mug.kg(-)(1).min(-)(1), 30 
      minutes). Furthermore, ex vivo studies showed that wortmannin, chelerythrine, or 
      apocynin abrogated the NMDAR-mediated vascular nitric oxide (NO) and ROS 
      generation and NOX activation in the vasculature. These findings implicate 
      vascular PI3K/Akt-protein kinase C signaling in the peripheral NMDAR-mediated 
      increases in vascular NO and NOX activation (ROS), which ultimately lead to 
      calcium influx and pressor response in conscious rats.
FAU - McGee, Marie A
AU  - McGee MA
AD  - Department of Pharmacology, Brody School of Medicine, East Carolina University, 
      Greenville, NC.
FAU - Abdel-Rahman, Abdel A
AU  - Abdel-Rahman AA
LA  - eng
GR  - R01 AA007839/AA/NIAAA NIH HHS/United States
GR  - R29 AA007839/AA/NIAAA NIH HHS/United States
GR  - 2R01 AA07839-19/AA/NIAAA NIH HHS/United States
GR  - AA07839-18S/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Aorta/drug effects
MH  - Blood Pressure/*drug effects
MH  - Calcium Signaling/drug effects
MH  - Male
MH  - Nitric Oxide/*physiology
MH  - Oxidative Stress/drug effects
MH  - Peripheral Nerves/drug effects
MH  - Phosphatidylinositol 3-Kinases/drug effects/*physiology
MH  - Protein Kinase C/antagonists & inhibitors
MH  - Proto-Oncogene Proteins c-akt/drug effects/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*physiology
MH  - Signal Transduction
PMC - PMC4013219
MID - NIHMS545275
EDAT- 2013/12/18 06:00
MHDA- 2014/12/30 06:00
PMCR- 2015/05/01
CRDT- 2013/12/17 06:00
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/12/30 06:00 [medline]
PHST- 2015/05/01 00:00 [pmc-release]
AID - 10.1097/FJC.0000000000000059 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2014 May;63(5):395-405. doi: 
      10.1097/FJC.0000000000000059.