Premium
Inhibition of Neutral Sphingomyelinase Prevents High Pressure‐Induced Shift in the Mediator of Endothelium‐Dependent Dilation from NO to H2O2
Author(s) -
Freed Julie K.,
Beyer Andreas M.,
Gutterman David D.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.901.1
Subject(s) - ceramide , sphingomyelin , chemistry , catalase , nitric oxide , hydrogen peroxide , mediator , medicine , contraction (grammar) , dilation (metric space) , blood pressure , endocrinology , biochemistry , oxidative stress , cholesterol , apoptosis , mathematics , combinatorics
We have shown that ceramide, a product of neutral sphingomyelinase, (N‐SMase) causes a transition from nitric oxide (NO) to hydrogen peroxide (H2O2) as the mediator of flow‐mediated dilation (FMD) in arterioles from healthy subjects. We tested the hypothesis that the stress of an elevation in intraluminal pressure similarly alters the mediator of FMD. Human arterioles (100–200μm diameter) were prepared for videomicroscopy. L‐NAME inhibited FMD (max dilation=24.6±7.6 vs. 82.6±4.9, n=6, p<0.01, *t‐test), whereas FMD was unaffected by L‐NAME following exposure to 150mmHg of intraluminal pressure (HP) for 30 min (71.8±5.9, n=7). Under control conditions, PEG‐Catalase (500 U) did not affect FMD (74.8±8.6, n=6), but after HP, FMD was reduced (23.8±6.1, n=6, p<0.01*). Treatment with the specific N‐SMase inhibitor GW4869 (4μM; 12 hours) did not alter FMD (79.9±11.3, n=3) vs. control (82.6±4.9, n=6), however FMD was attenuated post‐HP in the presence of GW4869 (33.9±6.7, n=3). Post‐HP, in GW4869‐treated vessels, FMD was blocked by L‐NAME (12.5±6.2, n=3) but tended to improve with catalase (48.6±9.4, n=3). These data suggest that N‐SMase is capable of altering the mechanism of FMD from NO to H2O2 following acute elevation of pressure.