Leukemia inhibitory factor relaxes arteries through endothelium-dependent mechanism.
Leukemia inhibitory factor (LIF) is a cytokine, which inhibits angiogenesis and decreases endothelial cell proliferation and migration, suggesting that LIF may modulate vascular tone. In this study, we examined the effects of LIF on the tone of rat arteries. The isometric tension of ring preparations from rat superior mesenteric arteries was continuously measured. LIF relaxed the mesenteric arteries in a dose-dependent manner, when the arterial rings were precontracted with phenylephrine. The relaxation was totally inhibited by mechanical removal of endothelium. N(G)-nitro-L-arginine methyl ester did not affect the relaxation by LIF. Ca(2+)-dependent K channel (KCa) blockers, apamin with charybdotoxin, inhibited the relaxation by LIF. Catalase, an enzyme which scavenges hydrogen peroxide, also inhibited the relaxation by LIF. Endothelium-derived hyperpolarizing factor relaxes smooth muscle cells and the effect is blocked by KCa and catalase. Our results suggest that LIF regulates vascular tone through the effect of this factor.
Kimura
Keizo
K
Department of Cadiovascular Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama 641-8510, Japan. kimura@wakayama-med.ac.jp
Tsuda
Kazushi
K
Moriwaki
Chizu
C
Kawabe
Tetsuya
T
Hamada
Masanori
M
Obana
Masahiro
M
Baba
Akira
A
Hano
Takuzo
T
Nishio
Ichiro
I
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001685:Biological Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020032:Tyrphostins / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D001685:Biological Factors; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D006634:Histamine H1 Antagonists; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D018727:Muscarinic Antagonists; D020032:Tyrphostins; D014662:Vasoconstrictor Agents; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C067410:endothelium-dependent hyperpolarization factor; D010656:Phenylephrine; D006861:Hydrogen Peroxide; D002374:Catalase; D019331:NG-Nitroarginine Methyl Ester