Inflammatory cytokines and rat vascular tone.
1. Experiments were performed to examine the effect of inflammatory cytokines, interleukin-2 (IL-2), IL-6 and IL-8, on the contractility of rat aorta. 2. Pretreatment of the endothelium-denuded aortic ring with IL-6 for 3 h caused a significant inhibition of its contraction (58.9 +/- 7.8%, n = 9, P < 0.01) when induced by 10(-6) mol/L phenylephrine. 3. On the other hand, IL-2 and IL-8 failed to show significant effects on the contractility of the aorta. 4. This inhibitory effect of IL-6 on phenylephrine-induced contraction showed dose-dependency, and completely disappeared in the presence of 10(-5) mol/L indomethacin. 5. In cultured rat vascular smooth muscle cells (VSMC), the release of 6-keto-prostaglandin F1alpha into the extracellular medium was significantly increased by exposure to IL-6, but not by exposure to IL-2 or IL-8. 6. IL-2, IL-6 and IL-8 showed no effects on the release of nitrite, a stable metabolite of nitric oxide (NO), from VSMC. 7. These results indicate that IL-6, not IL-2 or IL-8, is a potent inhibitor of the alpha-adrenergic-stimulated contraction of vascular smooth muscle and its action is mediated by the increased synthesis of prostacyclin rather than NO.
Ohkawa
F
F
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Ikeda
U
U
Kanbe
T
T
Kawasaki
K
K
Shimada
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D018836:Inflammation Mediators; D007378:Interleukins; D009573:Nitrites; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D007213:Indomethacin