Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

H2O2 is the transferrable factor mediating flow-induced dilation in human coronary arterioles. Circ Res 2011 Mar 04;108(5):566-73

Date

01/15/2011

Pubmed ID

21233456

Pubmed Central ID

PMC3108183

DOI

10.1161/CIRCRESAHA.110.237636

Scopus ID

2-s2.0-79952751560   117 Citations

Abstract

RATIONALE: Endothelial derived hydrogen peroxide (H(2)O(2)) is a necessary component of the pathway regulating flow-mediated dilation (FMD) in human coronary arterioles (HCAs). However, H(2)O(2) has never been shown to be the endothelium-dependent transferrable hyperpolarization factor (EDHF) in response to shear stress.

OBJECTIVE: We examined the hypothesis that H(2)O(2) serves as the EDHF in HCAs to shear stress.

METHODS AND RESULTS: Two HCAs were cannulated in series (a donor intact vessel upstream and endothelium-denuded detector vessel downstream). Diameter changes to flow were examined in the absence and presence of polyethylene glycol catalase (PEG-CAT). The open state probability of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels in smooth muscle cells downstream from the perfusate from an endothelium-intact arteriole was examined by patch clamping. In some experiments, a cyanogen bromide-activated resin column bound with CAT was used to remove H(2)O(2) from the donor vessel. When flow proceeds from donor to detector, both vessels dilate (donor:68±7%; detector: 45±11%). With flow in the opposite direction, only the donor vessel dilates. PEG-CAT contacting only the detector vessel blocked FMD in that vessel (6±4%) but not in donor vessel (61±13%). Paxilline inhibited dilation of endothelium-denuded HCAs to H(2)O(2). Effluent from donor vessels elicited K(+) channel opening in an iberiotoxin- or PEG-CAT-sensitive fashion in cell-attached patches but had little effect on channel opening on inside-out patches. Vasodilation of detector vessels was diminished when exposed to effluent from CAT-column.

CONCLUSIONS: Flow induced endothelial production of H(2)O(2), which acts as the transferrable EDHF activating BK(Ca) channels on the smooth muscle cells.

Author List

Liu Y, Bubolz AH, Mendoza S, Zhang DX, Gutterman DD

Authors

David D. Gutterman MD Sr Associate Director, Professor in the Medicine department at Medical College of Wisconsin
David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Arterioles
Biological Factors
Catalase
Coronary Vessels
Endothelium, Vascular
Humans
Hydrogen Peroxide
Indoles
Large-Conductance Calcium-Activated Potassium Channels
Muscle, Smooth, Vascular
Patch-Clamp Techniques
Polyethylene Glycols
Potassium Channel Blockers
Regional Blood Flow
Vasodilation
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a