title: Inhibitory effect of D3 dopamine receptor on migration of vascular smooth muscle cells induced by synergistic effect of angiotensin II and aldosterone.
abstract: OBJECTIVE
  The abnormal migration of vascular smooth muscle cells (VSMCs) has been implicated to contribute to lesion formation in the adult vasculature. The renin-angiotensin-aldosterone system (RAAS) is intensively involved in the pathogenesis of a variety of cardiovascular diseases. There are increasing pieces of evidence for interactions between RAAS and dopamine receptors. We hypothesize that the D3 receptor has an inhibitory effect on angiotensin II (Ang II)/aldosterone-induced VSMC migration.
  
  
  METHODS
  In this study, embryonic thoracic aortic smooth muscle cells were cultured. VSMC migration was determined by the Boyden chamber and wound healing assays.
  
  
  RESULTS
  VSMC migration was increased by Ang II (10(-10)-10(-7) mol/L) in a concentration-dependent manner, but not by aldosterone (10(-10)-10(-7) mol/L), and a synergistic effect of Ang II (10(-10) mol/L)/aldosterone (10(-10)mol/L) was also observed in VSMC migration. The migratory effects of Ang II alone/with aldosterone were attenuated by the activation of D3 receptors (10(-10)-10(-7) mol/L), although a D3 receptor agonist, PD128907, by itself, had no effect on VSMC migration. The inhibitory effect of the D3 receptor on Ang II/ aldosterone-mediated VSMC migration was blocked by the blocker of PKA (14-22 amide, 10(-7) mol/L), indicating that PKA was involved in the signaling pathway.
  
  
  CONCLUSIONS
  These results indicate that activation of vascular D3 receptors inhibits Ang II/aldosterone-induced VSMC migration through the PKA signal pathway, which may be important in the regulation of vascular remodeling.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University , Chongqing , PR China and.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Caiyu
authors.initials: C
authors.lastname: Chen
authors.forename: Duofen
authors.initials: D
authors.lastname: He
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004357:Drug Synergism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D050637:Receptors, Dopamine D3; D000804:Angiotensin II; D000450:Aldosterone
keywords: Aldosterone; angiotensin II; dopamine D3 receptor; migration; vascular smooth muscle cells