- 期刊
Endothelium Dependent and Independent Relaxations Induced by Ceramide in Vascular Smooth Muscles
並列摘要
The second messenger of sphingomyelin signaling, ceramide, acts as an intracellular signal via phosphatase activation and protein kinase C (PKC) inhibition. We tested the hypothesis that ceramide may have an regulatory role in determining vascular tone. Natural ceramide was applied to phenylephrine precontracted aortic rings from Sprague-Dawley rats in an organ bath. In endothelium-intact aortic rings, concentrations of ceramide at 10^(-6) and 10^(-5) mole/L induced 24±6 and 52±7% relaxation, respectively. Removal of the endothelium significantly inhibited ceramide-induced relaxation to 13±5%(10^(-6)mole/L) and 29±5% (10^(-5)mole/L). Similar inhibition was observed in endothelium-intact aortic rings pretreated with N(superscript ω)-nitro-L-arginine (10^(-4)mole/L) or methylene blue (10^(-5)mole/L), suggestingthat endothelium-derived nitric oxide is involved in ceramide-induced relaxation. N-acetylsphingosine (C2-ceramide), N-hexanoylsphingosine (C6-ceramide), N-palmitoylsphingosine (C16-ceramide)and D-sphingosine all demonstrated dose-dependent relaxation responses in endothelium-intact vessels. Sphingomyelin signaling through the nitric oxide-dependent mechanism may have an important role in regulating vascular tone.
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