title: Adiponectin at Physiologically Relevant Concentrations Enhances the Vasorelaxative Effect of Acetylcholine via Cav-1/AdipoR-1 Signaling.
abstract: Clinical studies have identified hypoadiponectinemia as an independent hypertension risk factor. It is known that adiponectin (APN) can directly cause vasodilation, but the doses required exceed physiologic levels several fold. In the current study, we determine the effect of physiologically relevant APN concentrations upon vascular tone, and investigate the mechanism(s) responsible. Physiologic APN concentrations alone induced no significant vasorelaxation. Interestingly, pretreatment of wild type mouse aortae with physiologic APN levels significantly enhanced acetylcholine (ACh)-induced vasorelaxation (P<0.01), an endothelium-dependent and nitric oxide (NO)-mediated process. Knockout of adiponectin receptor 1 (AdipoR1) or caveolin-1 (Cav-1, a cell signaling facilitating molecule), but not adiponectin receptor 2 (AdipoR2) abolished APN-enhanced ACh-induced vasorelaxation. Immunoblot assay revealed APN promoted the AdipoR1/Cav1 signaling complex in human endothelial cells. Treatment of HUVECs with physiologic APN concentrations caused significant eNOS phosphorylation and nitric oxide (NO) production (P<0.01), an effect abolished in knockdown of either AdipoR1 or Cav-1. Taken together, these data demonstrate for the first time physiologic APN levels enhance the vasorelaxative response to ACh by inducing NO production through AdipoR1/Cav-1 mediated signaling. In physiologic conditions, APN plays an important function of maintaining vascular tone.
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, China.|Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States of America.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Physiology, National Key Discipline and Key Laboratory of Cytophysiology of Shanxi Province, Shanxi Medical University, Shanxi, 030001, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States of America.
authors.forename: Wayne Bigond
authors.initials: WB
authors.lastname: Lau
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States of America.
authors.forename: Jianli
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States of America.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lopez
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States of America.
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Christopher
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, China.|Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States of America.
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Ma
authors.affiliation: Department of Physiology, National Key Discipline and Key Laboratory of Cytophysiology of Shanxi Province, Shanxi Medical University, Shanxi, 030001, China.|Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States of America.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D054419:Receptors, Adiponectin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D052242:Adiponectin; D051242:Caveolin 1; D054419:Receptors, Adiponectin; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine