title: Selective involvement of serum response factor in pressure-induced myogenic tone in resistance arteries.
abstract: OBJECTIVE
  In resistance arteries, diameter adjustment in response to pressure changes depends on the vascular cytoskeleton integrity. Serum response factor (SRF) is a dispensable transcription factor for cellular growth, but its role remains unknown in resistance arteries. We hypothesized that SRF is required for appropriate microvascular contraction.
  
  
  RESULTS
  We used mice in which SRF was specifically deleted in smooth muscle or endothelial cells, and their control. Myogenic tone and pharmacological contraction was determined in resistance arteries. mRNA and protein expression were assessed by quantitative real-time PCR (qRT-PCR) and Western blot. Actin polymerization was determined by confocal microscopy. Stress-activated channel activity was measured by patch clamp. Myogenic tone developing in response to pressure was dramatically decreased by SRF deletion (5.9±2.3%) compared with control (16.3±3.2%). This defect was accompanied by decreases in actin polymerization, filamin A, myosin light chain kinase and myosin light chain expression level, and stress-activated channel activity and sensitivity in response to pressure. Contractions induced by phenylephrine or U46619 were not modified, despite a higher sensitivity to p38 blockade; this highlights a compensatory pathway, allowing normal receptor-dependent contraction.
  
  
  CONCLUSIONS
  This study shows for the first time that SRF has a major part to play in the control of local blood flow via its central role in pressure-induced myogenic tone in resistance arteries.
authors.affiliation: CNRS UMR 6214 - INSERM U1083, Université d'Angers, Faculté de Médecine, 49045 Angers, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Retailleau
authors.forename: Bertrand
authors.initials: B
authors.lastname: Toutain
authors.forename: Guillaume
authors.initials: G
authors.lastname: Galmiche
authors.forename: Céline
authors.initials: C
authors.lastname: Fassot
authors.forename: Reza
authors.initials: R
authors.lastname: Sharif-Naeini
authors.forename: Gilles
authors.initials: G
authors.lastname: Kauffenstein
authors.forename: Mathias
authors.initials: M
authors.lastname: Mericskay
authors.forename: Fabrice
authors.initials: F
authors.lastname: Duprat
authors.forename: Linda
authors.initials: L
authors.lastname: Grimaud
authors.forename: Jean
authors.initials: J
authors.lastname: Merot
authors.forename: Aurelie
authors.initials: A
authors.lastname: Lardeux
authors.forename: Anne
authors.initials: A
authors.lastname: Pizard
authors.forename: Véronique
authors.initials: V
authors.lastname: Baudrie
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Göthert
authors.forename: Patrick
authors.initials: P
authors.lastname: Lacolley
authors.forename: Daniel
authors.initials: D
authors.lastname: Henrion
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Li
authors.forename: Laurent
authors.initials: L
authors.lastname: Loufrani
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001158:Arteries / Q000378:metabolism; D015153:Blotting, Western; D020013:Calcium Signaling; D003285:Contractile Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D064448:Filamins; D005786:Gene Expression Regulation; D008297:Male; D040542:Mechanotransduction, Cellular; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009213:Myography; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D018408:Patch-Clamp Techniques; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026362:Serum Response Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013623:Tail / Q000098:blood supply*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000199:Actins; D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D018994:Myosin Light Chains; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D026362:Serum Response Factor; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009219:Myosin-Light-Chain Kinase; D048051:p38 Mitogen-Activated Protein Kinases