Endothelium dependent and independent relaxations induced by ceramide in vascular smooth muscles.
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 omega-nitro-L-arginine (10(-4) mole/L) or methylene blue (10(-5) mole/L), suggesting that 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.
Department of Physiology, National Defense Medical Center, Taipei, Taiwan, ROC.
J S
JS
Jin
C S
CS
Tsai
X
X
Si
R C
RC
Webb
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D002518:Ceramides / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013109:Sphingomyelins / Q000494:pharmacology
D002518:Ceramides; D013109:Sphingomyelins; D009569:Nitric Oxide; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases