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Ceramide reduces endothelium-dependent vasodilation by increasing superoxide production in small bovine coronary arteries. Circ Res 2001 Apr 27;88(8):824-31

Date

04/28/2001

Pubmed ID

11325875

DOI

10.1161/hh0801.089604

Scopus ID

2-s2.0-0035957592   64 Citations

Abstract

Ceramide serves as a second messenger in a variety of mammalian cells. Little is known regarding the role of ceramide in the regulation of vascular endothelial function. The present study was designed to determine whether ceramide affects endothelium-dependent vasodilation in coronary arteries and to explore the mechanism of action of ceramide. In isolated and pressurized small bovine coronary arteries, cell-permeable C(2)-ceramide (10(-)(5) mol/L) markedly attenuated vasodilator responses to bradykinin and A23187 (by 40% and 60%, respectively). In the presence of K(G)-nitro-L-arginine methyl ester, ceramide produced no further inhibition on the vasodilation induced by these vasodilators. Ceramide had no effect on DETA NONOate-induced vasodilation. By use of a fluorescence NO indicator (4,5-diaminofluorescein diacetate), intracellular NO was measured in the endothelium of freshly isolated small coronary arteries. It was found that ceramide significantly inhibited bradykinin-induced NO increase within endothelial cells. However, it had no effect on the activity of arterial or endothelial NO synthase. Pretreatment of the arteries with sodium dihydroxybenzene disulfonate (Tiron, 10(-)(3) mol/L), a cell-permeable superoxide scavenger, or polyethylene glycol superoxide dismutase (100 U/mL) largely restored the inhibitory effects of ceramide on the vasodilation and NO increase induced by bradykinin or A23187. Moreover, ceramide time-dependently increased intracellular superoxide (O(2)(-. )) in the endothelium, as measured by a fluorescent O(2)(-. )indicator, dihydroethidium. These results demonstrate that ceramide inhibits endothelium-dependent vasodilation in small coronary arteries by decreasing NO in vascular endothelial cells and that this decrease in NO is associated with increased O(2)(-. ) but not with the inhibition of NO synthase activity within these cells.

Author List

Zhang DX, Zou AP, Li PL

Author

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

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
Animals
Arteries
Bradykinin
Calcimycin
Cattle
Ceramides
Citrulline
Coronary Vessels
Endothelium, Vascular
Enzyme Inhibitors
Fluorescent Dyes
Free Radical Scavengers
In Vitro Techniques
Intracellular Fluid
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Sphingosine
Superoxide Dismutase
Superoxides
Vasodilation
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