PMID- 12574154
OWN - NLM
STAT- MEDLINE
DCOM- 20030214
LR  - 20190706
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 92
IP  - 2
DP  - 2003 Feb 7
TI  - Role for hydrogen peroxide in flow-induced dilation of human coronary arterioles.
PG  - e31-40
AB  - Flow-induced dilation (FID) is dependent largely on hyperpolarization of vascular 
      smooth muscle cells (VSMCs) in human coronary arterioles (HCA) from patients with 
      coronary disease. Animal studies show that shear stress induces endothelial 
      generation of hydrogen peroxide (H2O2), which is proposed as an 
      endothelium-derived hyperpolarizing factor (EDHF). We tested the hypothesis that 
      H2O2 contributes to FID in HCA. Arterioles (135+/-7 micro m, n=71) were dissected 
      from human right atrial appendages at the time of cardiac surgery and cannulated 
      with glass micropipettes. Changes in internal diameter and membrane potential of 
      VSMCs to shear stress, H2O2, or to papaverine were recorded with videomicroscopy. 
      In some vessels, endothelial H2O2 generation to shear stress was monitored 
      directly using confocal microscopy with 2',7'-dichlorofluorescin diacetate (DCFH) 
      or using electron microscopy with cerium chloride. Catalase inhibited FID (%max 
      dilation; 66+/-8 versus 25+/-7%; P<0.05, n=6), whereas dilation to papaverine was 
      unchanged. Shear stress immediately increased DCFH fluorescence in the 
      endothelial cell layer, whereas treatment with catalase abolished the increase in 
      fluorescence. Electron microscopy with cerium chloride revealed shear 
      stress-induced increase in cerium deposition in intimal area surrounding 
      endothelial cells. Exogenous H2O2 dilated (%max dilation; 97+/-1%, ED50; 
      3.0+/-0.7x10(-5) mol/L) and hyperpolarized HCA. Dilation to H2O2 was reduced by 
      catalase, 40 mmol/L KCl, or charybdotoxin plus apamin, whereas endothelial 
      denudation, deferoxamine, 1H-(1,2,4)-oxadiazole-[4,3-a]quinoxalin-1-one, or 
      glibenclamide had no effect. These data provide evidence that shear stress 
      induces endothelial release of H2O2 and are consistent with the idea that H2O2 is 
      an EDHF that contributes to FID in HCA from patients with heart disease. The full 
      text of this article is available at http://www.circresaha.org.
FAU - Miura, Hiroto
AU  - Miura H
AD  - Department of Veterans Affairs Medical Center, Milwaukee, Wis 53226, USA. 
      hmiura@mcw.edu
FAU - Bosnjak, John J
AU  - Bosnjak JJ
FAU - Ning, Gang
AU  - Ning G
FAU - Saito, Takashi
AU  - Saito T
FAU - Miura, Mamoru
AU  - Miura M
FAU - Gutterman, David D
AU  - Gutterman DD
LA  - eng
GR  - HL62852/HL/NHLBI NIH HHS/United States
GR  - HL65203/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Iron Chelating Agents)
RN  - 0 (Oxidants)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Vasodilator Agents)
RN  - 24345-16-2 (Apamin)
RN  - 30K4522N6T (Cerium)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - DAA13NKG2Q (Papaverine)
RN  - EC 1.11.1.6 (Catalase)
RN  - SX6K58TVWC (Glyburide)
SB  - IM
MH  - Apamin/pharmacology
MH  - Arterioles/drug effects/*physiology/ultrastructure
MH  - Catalase/pharmacology
MH  - Cerium
MH  - Coronary Vessels/drug effects/*physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Fluorescent Dyes
MH  - Glyburide/pharmacology
MH  - Humans
MH  - Hydrogen Peroxide/*metabolism/pharmacology
MH  - In Vitro Techniques
MH  - Iron Chelating Agents/pharmacology
MH  - Membrane Potentials/drug effects/physiology
MH  - Microscopy, Confocal
MH  - Microscopy, Electron
MH  - Microscopy, Video
MH  - Muscle, Smooth, Vascular/drug effects/metabolism/ultrastructure
MH  - Oxidants/*metabolism/pharmacology
MH  - Papaverine/pharmacology
MH  - Potassium Channel Blockers/pharmacology
MH  - Stress, Mechanical
MH  - Vasodilation/drug effects/*physiology
MH  - Vasodilator Agents/pharmacology
EDAT- 2003/02/08 04:00
MHDA- 2003/02/15 04:00
CRDT- 2003/02/08 04:00
PHST- 2003/02/08 04:00 [pubmed]
PHST- 2003/02/15 04:00 [medline]
PHST- 2003/02/08 04:00 [entrez]
AID - 10.1161/01.res.0000054200.44505.ab [doi]
PST - ppublish
SO  - Circ Res. 2003 Feb 7;92(2):e31-40. doi: 10.1161/01.res.0000054200.44505.ab.