title: Vascular Actions of Angiotensin 1-7 in the Human Microcirculation: Novel Role for Telomerase.
abstract: This study examined vascular actions of angiotensin 1-7 (ANG 1-7) in human atrial and adipose arterioles.
  
  
  
  The endothelium-derived hyperpolarizing factor of flow-mediated dilation (FMD) switches from antiproliferative nitric oxide (NO) to proatherosclerotic hydrogen peroxide in arterioles from humans with coronary artery disease (CAD). Given the known vasoprotective properties of ANG 1-7, we tested the hypothesis that overnight ANG 1-7 treatment restores the NO component of FMD in arterioles from patients with CAD. Endothelial telomerase activity is essential for preserving the NO component of vasodilation in the human microcirculation; thus, we also tested whether telomerase activity was necessary for ANG 1-7-mediated vasoprotection by treating separate arterioles with ANG 1-7±the telomerase inhibitor 2-[[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-yl]amino]benzoic acid. ANG 1-7 dilated arterioles from patients without CAD, whereas dilation was significantly reduced in arterioles from patients with CAD. In atrial arterioles from patients with CAD incubated with ANG 1-7 overnight, the NO synthase inhibitor NG-nitro-l-arginine methyl ester abolished FMD, whereas the hydrogen peroxide scavenger polyethylene glycol catalase had no effect. Conversely, in vessels incubated with ANG 1-7+2-[[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-yl]amino]benzoic acid, NG-nitro-l-arginine methyl ester had no effect on FMD, but polyethylene glycol catalase abolished dilation. In cultured human coronary artery endothelial cells, ANG 1-7 significantly increased telomerase activity. These results indicate that ANG 1-7 dilates human microvessels, and dilation is abrogated in the presence of CAD. Furthermore, ANG 1-7 treatment is sufficient to restore the NO component of FMD in arterioles from patients with CAD in a telomerase-dependent manner.
  
  
  
  ANG 1-7 exerts vasoprotection in the human microvasculature via modulation of telomerase activity.
authors.affiliation: From the Department of Physical Medicine and Rehabilitation (M.J.D.), Department of Medicine, Cardiovascular Center (M.J.D., N.S.Z., M.R., D.D.G., V.L.N., A.M.B.), Department of Pathology, Division of Pediatric Pathology (V.K.S., P.E.N.), Department of Plastic Surgery (J.B.H.), Department of Cardiothoracic Surgery (C.F.R.), and Department of Physiology (A.M.B.), Medical College of Wisconsin, Milwaukee; and Department of Health and Medicine, Carroll University, Waukesha, WI (N.S.Z.).
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Durand
authors.affiliation: From the Department of Physical Medicine and Rehabilitation (M.J.D.), Department of Medicine, Cardiovascular Center (M.J.D., N.S.Z., M.R., D.D.G., V.L.N., A.M.B.), Department of Pathology, Division of Pediatric Pathology (V.K.S., P.E.N.), Department of Plastic Surgery (J.B.H.), Department of Cardiothoracic Surgery (C.F.R.), and Department of Physiology (A.M.B.), Medical College of Wisconsin, Milwaukee; and Department of Health and Medicine, Carroll University, Waukesha, WI (N.S.Z.).
authors.forename: Natalya S
authors.initials: NS
authors.lastname: Zinkevich
authors.affiliation: From the Department of Physical Medicine and Rehabilitation (M.J.D.), Department of Medicine, Cardiovascular Center (M.J.D., N.S.Z., M.R., D.D.G., V.L.N., A.M.B.), Department of Pathology, Division of Pediatric Pathology (V.K.S., P.E.N.), Department of Plastic Surgery (J.B.H.), Department of Cardiothoracic Surgery (C.F.R.), and Department of Physiology (A.M.B.), Medical College of Wisconsin, Milwaukee; and Department of Health and Medicine, Carroll University, Waukesha, WI (N.S.Z.).
authors.forename: Michael
authors.initials: M
authors.lastname: Riedel
authors.affiliation: From the Department of Physical Medicine and Rehabilitation (M.J.D.), Department of Medicine, Cardiovascular Center (M.J.D., N.S.Z., M.R., D.D.G., V.L.N., A.M.B.), Department of Pathology, Division of Pediatric Pathology (V.K.S., P.E.N.), Department of Plastic Surgery (J.B.H.), Department of Cardiothoracic Surgery (C.F.R.), and Department of Physiology (A.M.B.), Medical College of Wisconsin, Milwaukee; and Department of Health and Medicine, Carroll University, Waukesha, WI (N.S.Z.).
authors.forename: David D
authors.initials: DD
authors.lastname: Gutterman
authors.affiliation: From the Department of Physical Medicine and Rehabilitation (M.J.D.), Department of Medicine, Cardiovascular Center (M.J.D., N.S.Z., M.R., D.D.G., V.L.N., A.M.B.), Department of Pathology, Division of Pediatric Pathology (V.K.S., P.E.N.), Department of Plastic Surgery (J.B.H.), Department of Cardiothoracic Surgery (C.F.R.), and Department of Physiology (A.M.B.), Medical College of Wisconsin, Milwaukee; and Department of Health and Medicine, Carroll University, Waukesha, WI (N.S.Z.).
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Nasci
authors.affiliation: From the Department of Physical Medicine and Rehabilitation (M.J.D.), Department of Medicine, Cardiovascular Center (M.J.D., N.S.Z., M.R., D.D.G., V.L.N., A.M.B.), Department of Pathology, Division of Pediatric Pathology (V.K.S., P.E.N.), Department of Plastic Surgery (J.B.H.), Department of Cardiothoracic Surgery (C.F.R.), and Department of Physiology (A.M.B.), Medical College of Wisconsin, Milwaukee; and Department of Health and Medicine, Carroll University, Waukesha, WI (N.S.Z.).
authors.forename: Valerie K
authors.initials: VK
authors.lastname: Salato
authors.affiliation: From the Department of Physical Medicine and Rehabilitation (M.J.D.), Department of Medicine, Cardiovascular Center (M.J.D., N.S.Z., M.R., D.D.G., V.L.N., A.M.B.), Department of Pathology, Division of Pediatric Pathology (V.K.S., P.E.N.), Department of Plastic Surgery (J.B.H.), Department of Cardiothoracic Surgery (C.F.R.), and Department of Physiology (A.M.B.), Medical College of Wisconsin, Milwaukee; and Department of Health and Medicine, Carroll University, Waukesha, WI (N.S.Z.).
authors.forename: John B
authors.initials: JB
authors.lastname: Hijjawi
authors.affiliation: From the Department of Physical Medicine and Rehabilitation (M.J.D.), Department of Medicine, Cardiovascular Center (M.J.D., N.S.Z., M.R., D.D.G., V.L.N., A.M.B.), Department of Pathology, Division of Pediatric Pathology (V.K.S., P.E.N.), Department of Plastic Surgery (J.B.H.), Department of Cardiothoracic Surgery (C.F.R.), and Department of Physiology (A.M.B.), Medical College of Wisconsin, Milwaukee; and Department of Health and Medicine, Carroll University, Waukesha, WI (N.S.Z.).
authors.forename: Charles F
authors.initials: CF
authors.lastname: Reuben
authors.affiliation: From the Department of Physical Medicine and Rehabilitation (M.J.D.), Department of Medicine, Cardiovascular Center (M.J.D., N.S.Z., M.R., D.D.G., V.L.N., A.M.B.), Department of Pathology, Division of Pediatric Pathology (V.K.S., P.E.N.), Department of Plastic Surgery (J.B.H.), Department of Cardiothoracic Surgery (C.F.R.), and Department of Physiology (A.M.B.), Medical College of Wisconsin, Milwaukee; and Department of Health and Medicine, Carroll University, Waukesha, WI (N.S.Z.).
authors.forename: Paula E
authors.initials: PE
authors.lastname: North
authors.affiliation: From the Department of Physical Medicine and Rehabilitation (M.J.D.), Department of Medicine, Cardiovascular Center (M.J.D., N.S.Z., M.R., D.D.G., V.L.N., A.M.B.), Department of Pathology, Division of Pediatric Pathology (V.K.S., P.E.N.), Department of Plastic Surgery (J.B.H.), Department of Cardiothoracic Surgery (C.F.R.), and Department of Physiology (A.M.B.), Medical College of Wisconsin, Milwaukee; and Department of Health and Medicine, Carroll University, Waukesha, WI (N.S.Z.). abeyer@mcw.edu.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Beyer
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply*; D000368:Aged; D000803:Angiotensin I / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000201:enzymology / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006325:Heart Atria; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000819:agonists / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000803:Angiotensin I; C509186:TERT protein, human; D019098:Telomerase; C118790:angiotensin I (1-7)
keywords: coronary artery disease; microcirculation; nitric oxide; telomerase; vasodilation