Inhibitory effect of interleukin-6 on vascular smooth muscle contraction.
Our objective was to investigate the direct effect of interleukin-6 (IL-6) on the vascular smooth muscle contraction. We measured the contraction of endothelium-denuded aortic rings isolated from Sprague-Dawley rats. We also investigated the involvement of vasodilator prostaglandin and guanosine 3',5'-cyclic monophosphate (cGMP) productions in the effect of IL-6 using cultured rat vascular smooth muscle cells (VSMC). Exposing the aortic rings to recombinant murine IL-6 (50 U/ml) for 180 min significantly suppressed the phenylephrine (10(-9)-10(-5) M)-induced contraction. This inhibitory effect of IL-6 on the contraction tended to exhibit a dose-dependent relationship (0.5-50 U/ml). The effect of IL-6 was totally eliminated in the presence of indomethacin (10(-5) M). The release of immunoreactive 6-ketoprostaglandin F1 alpha from cultured rat VSMC was significantly increased by exposure to IL-6. Intracellular cGMP concentration in VSMC was not affected by IL-6. In conclusion, IL-6 is a potent inhibitor of the alpha-adrenergic-stimulated contraction of vascular smooth muscle. Its action is endothelium independent and mediated by the increased synthesis of prostacyclin in VSMC.
Ohkawa
F
F
Department of Community and Family Medicine, Jichi Medical School, Tochigi, Japan.
Ikeda
U
U
Kawasaki
K
K
Kusano
E
E
Igarashi
M
M
Shimada
K
K
D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009994:Osmolar Concentration; D010656:Phenylephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
D007375:Interleukin-1; D015850:Interleukin-6; D011453:Prostaglandins; D010656:Phenylephrine; D006152:Cyclic GMP; D007213:Indomethacin