title: Irisin relaxes mouse mesenteric arteries through endothelium-dependent and endothelium-independent mechanisms.
abstract: Irisin, a newly discovered myokine, has been shown to produce modest weight loss and improve glucose intolerance in mice. The purpose of this study was to investigate the effects of irisin on vascular activity and the mechanisms involved. Experiments were performed on mouse mesenteric arteries. We demonstrated that irisin induced relaxation in mesenteric arteries with or without endothelium in a concentration-dependent manner. It was further demonstrated that the irisin-induced vasorelaxation effects on endothelium-intact mesenteric arteries were reduced by pretreatment with Nω-nitro-L-arginine methyl ester (L-NAME) or 1H-[1, 2, 4] oxadizolo [4, 3-a] quinoxalin-1-one (ODQ). However, pretreatment with indomethacin (INDO), a nonselective cyclooxygenase inhibitor did not modulate irisin-induced relaxation. In addition, the contraction due to extracellular Ca(2+) influx and intracellular Ca(2+) release was also inhibited by irisin. In summary, these results suggested that the endothelium-dependent relaxation of irisin is mediated by the nitric oxide (NO)-guanosine 3', 5'-cyclic phosphate (cGMP)-dependent pathway but not the prostaglandin I2 (PGI2)-cyclic adenosine monophosphate (cAMP)-dependent mechanism. Endothelium-independent relaxation may be depend on inhibiting Ca(2+) influx through blocking VDCCs and intracellular Ca(2+) release through both IP3R and RyR channels.
authors.affiliation: Experimental Animal Center, The Second Hospital of Shandong University, Jinan 250012, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Clinical Medicine, School of Medicine, Shandong University, Jinan 250012, PR China.
authors.forename: Fangzhu
authors.initials: F
authors.lastname: Wan
authors.affiliation: Experimental Animal Center, The Second Hospital of Shandong University, Jinan 250012, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Clinical Medicine, School of Medicine, Shandong University, Jinan 250012, PR China. Electronic address: sduwuqi@hotmail.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D059289:Vascular Stiffness / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: C571428:FNDC5 protein, mouse; D005353:Fibronectins; D009569:Nitric Oxide; D006152:Cyclic GMP
keywords: Irisin; Mouse mesenteric artery; Vasorelaxation