title: Irisin Lowers Blood Pressure by Improvement of Endothelial Dysfunction via AMPK-Akt-eNOS-NO Pathway in the Spontaneously Hypertensive Rat.
abstract: Exercise is a major nonpharmacological treatment for hypertension, but its underlying mechanisms are still not completely elucidated. Irisin, a polypeptide containing 112 amino acids, which is secreted mainly by skeletal muscle cells during exercise, exerts a protective role in metabolic diseases, such as diabetes mellitus and obesity. Because of the close relationship between irisin and metabolic diseases, we hypothesized that irisin may play a role in the regulation of blood pressure.
  
  
  
  Blood pressures of male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were monitored through the carotid artery. Our study found that acute intravenous injection of irisin reduced blood pressure in SHRs, but not WKY rats. Irisin, by itself, had no direct vasorelaxing effect in phenylephrine-preconstricted mesenteric arteries from SHRs. However, irisin augmented the acetylcholine-induced vasorelaxation in mesenteric arteries from SHRs that could be reversed by Nω-nitro-l-arginine-methyl ester (L-NAME; 100 μmol/L), indicating a role of nitric oxide (NO) in this action. Indeed, irisin increased NO production and phosphorylation of endothelial nirtic oxide synthase (eNOS) in endothelial cells. 5'-AMP-activated protein kinase (AMPK) was involved in the vasorelaxing effect of irisin because compound C (20 μmol/L), an AMPK inhibitor, blocked the irisin-mediated increase in phosphorylation of eNOS and protein kinase B (Akt) in endothelial cells and vasodilation in mesenteric arteries.
  
  
  
  We conclude that acute administration of irisin lowers blood pressure of SHRs by amelioration of endothelial dysfunction of the mesenteric artery through the AMPK-Akt-eNOS-NO signaling pathway.
authors.affiliation: Department of Cardiology, Daping Hospital, Chongqing Institute of Cardiology, The Third Military Medical University, Chongqing, China.
authors.forename: Jinjuan
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Cardiology, Daping Hospital, Chongqing Institute of Cardiology, The Third Military Medical University, Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Cardiology, Daping Hospital, Chongqing Institute of Cardiology, The Third Military Medical University, Chongqing, China.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, Chongqing Institute of Cardiology, The Third Military Medical University, Chongqing, China.
authors.forename: Yukai
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Daping Hospital, Chongqing Institute of Cardiology, The Third Military Medical University, Chongqing, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, Daping Hospital, Chongqing Institute of Cardiology, The Third Military Medical University, Chongqing, China chunyuzeng01@163.com zhoulin@mail.tmmu.com.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Division of Renal Diseases & Hypertension, Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.affiliation: Department of Cardiology, Daping Hospital, Chongqing Institute of Cardiology, The Third Military Medical University, Chongqing, China chunyuzeng01@163.com zhoulin@mail.tmmu.com.cn.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000493:pharmacokinetics; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015854:Up-Regulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000493:pharmacokinetics
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; C583676:FNDC5 protein, rat; D005353:Fibronectins; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D055372:AMP-Activated Protein Kinases; D019331:NG-Nitroarginine Methyl Ester
keywords: 5‐AMP‐activated protein kinase; hypertension; irisin; nitric oxide; vasorelaxation