The role of the endothelium in ceramide-induced vasodilation.
Ceramide, a novel sphingomyelin-derived second messenger mediates cellular signals of cytokines such as tumor necrosis factor-alpha (TNF-alpha). In the present study, we hypothesized that the endothelium contributes to ceramide-induced vasodilation. We report that relaxation to ceramide in endothelium-intact rat thoracic aortic rings is greater than in endothelium-denuded or endothelial nitric oxide synthase (endothelial NO synthase)-inactivated rings. We conclude that the endothelium contributes to ceramide-induced relaxation possibly through an interaction between sphingomyelin hydrolysis and endothelial NO synthase within caveolae.
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA. dgjohns@umich.edu
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D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation
D004791:Enzyme Inhibitors; C064769:N-acetylsphingosine; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D013110:Sphingosine; D008751:Methylene Blue