PMID- 12574111
OWN - NLM
STAT- MEDLINE
DCOM- 20030310
LR  - 20211203
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 41
IP  - 2
DP  - 2003 Feb
TI  - Wall stiffness suppresses Akt/eNOS and cytoprotection in pulse-perfused 
      endothelium.
PG  - 378-81
AB  - Increased steady shear stress stimulates nitric oxide synthase (eNOS) in part by 
      Akt-dependent phosphorylation. Arteries in vivo are exposed to pulse perfusion 
      (PP) combining phasic shear with stretch. In compliant vessels, enhancing PP 
      lowers vascular tone by stimulating eNOS; whereas in aged, stiff arteries, 
      flow-mediated dilation declines and PP is a prominent risk factor. Here, we 
      tested the hypothesis that reduced wall distensibility alters PP-induced eNOS/Akt 
      mechano-signaling. Bovine aortic endothelial cells cultured within distensible 
      tubes were exposed to physiological nonreversing steady or PP (7 dynes/cm(2) mean 
      shear, pulse pressure 0 or 90 mm Hgx2 hours) in a custom servo-system. In 
      compliant tubes, PP doubled Akt phosphorylation above nonpulsatile flow levels, 
      whereas P-Akt declined to static levels from PP in stiffer tubes. eNOS 
      phosphorylation (S-1179) similarly increased with PP in compliant tubes but was 
      nearly undetectable with increased PP in stiffer tubes. After PP, brief exposure 
      of cells to ultraviolet irradiation (oxidant stress) and subsequent culture 
      revealed cytoprotection in compliant tubes but diffuse cytotoxicity and cell 
      detachment in stiffer tubes. NOS inhibition by L-NAME converted compliant-tube 
      post-UV behavior to that of stiffer tubes. These data provide novel evidence that 
      wall compliance can directionally mediate endothelial Akt/eNOS phosphorylation 
      and mechano-signaling. This may help explain increased vascular risks resulting 
      from artery stiffening.
FAU - Peng, Xinqi
AU  - Peng X
AD  - Division of Cardiology, Department of Medicine, Johns Hopkins Medical 
      Institutions, Baltimore, MD 21287, USA.
FAU - Haldar, Saptarsi
AU  - Haldar S
FAU - Deshpande, Shailesh
AU  - Deshpande S
FAU - Irani, Kaikobad
AU  - Irani K
FAU - Kass, David A
AU  - Kass DA
LA  - eng
GR  - HL-47511/HL/NHLBI NIH HHS/United States
GR  - HL-65608/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Animals
MH  - Cell Adhesion/drug effects/radiation effects
MH  - Cell Division/drug effects/radiation effects
MH  - Cell Line
MH  - Endothelium, Vascular/*metabolism/pathology
MH  - Enzyme Inhibitors/pharmacology
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide Synthase/antagonists & inhibitors/*metabolism
MH  - Nitric Oxide Synthase Type III
MH  - Pressure
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
EDAT- 2003/02/08 04:00
MHDA- 2003/03/11 04:00
CRDT- 2003/02/08 04:00
PHST- 2003/02/08 04:00 [pubmed]
PHST- 2003/03/11 04:00 [medline]
PHST- 2003/02/08 04:00 [entrez]
AID - 10.1161/01.hyp.0000049624.99844.3d [doi]
PST - ppublish
SO  - Hypertension. 2003 Feb;41(2):378-81. doi: 10.1161/01.hyp.0000049624.99844.3d.