title: Prolonged vasoconstriction of resistance arteries involves vascular smooth muscle actin polymerization leading to inward remodelling.
abstract: OBJECTIVE
  Inward remodelling of the resistance vasculature is predictive of hypertension and life-threatening cardiovascular events. We hypothesize that the contractile mechanisms responsible for maintaining a reduced diameter over time in response to prolonged stimulation with vasoconstrictor agonists are in part responsible for the initial stages of the remodelling process. Here we investigated the role of vascular smooth muscle (VSM) actin polymerization on agonist-induced vasoconstriction and development of inward remodelling.
  
  
  RESULTS
  Experiments were conducted in Sprague-Dawley rat resistance vessels isolated from the cremaster and mesentery. Within blood vessels, actin dynamics of VSM were monitored by confocal microscopy after introduction of fluorescent actin monomers through electroporation and by differential centrifugation to probe globular (G) and filamentous (F) actin content. Results indicated that 4 h of agonist-dependent vasoconstriction induced inward remodelling and caused significant actin polymerization, elevating the F-/total-actin ratio. Inhibition of actin polymerization prevented vessels from maintaining prolonged vasoconstriction and developing inward remodelling. Activation of the small GTPases Rho/Rac/Cdc42 also increased the F-/total-actin ratio and induced inward remodelling, while inhibition of Rho kinase or Rac-1 prevented inward remodelling. Disruption of the actin cytoskeleton reversed the inward remodelling caused by prolonged vasoconstriction, but did not affect the passive diameter of freshly isolated vessels.
  
  
  CONCLUSIONS
  These results indicate that vasoconstriction-induced inward remodelling is in part caused by the polymerization of actin within VSM cells through activation of small GTPases.
authors: Dalton Cardiovascular Research Center, University of Missouri-Columbia, 134 Research Park Dr, Columbia, MO 65211, USA.
authors: Marius C
authors: MC
authors: Staiculescu
authors: Edgar L
authors: EL
authors: Galiñanes
authors: Guiling
authors: G
authors: Zhao
authors: Uri
authors: U
authors: Ulloa
authors: Minshan
authors: M
authors: Jin
authors: Mirza I
authors: MI
authors: Beig
authors: Gerald A
authors: GA
authors: Meininger
authors: Luis A
authors: LA
authors: Martinez-Lemus
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000199:Actins / Q000378:metabolism*; D000818:Animals; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D058105:Polymerization; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000199:Actins; D047428:Protein Kinase Inhibitors; D014662:Vasoconstrictor Agents; D054460:rho-Associated Kinases; C499134:Rac1 protein, rat; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins
keywords: Cytoskeletal remodelling; Hypertension; Microcirculation; Rac-1; Rho-kinase