title: Leptin inhibits the proliferation of vascular smooth muscle cells induced by angiotensin II through nitric oxide-dependent mechanisms.
abstract: OBJECTIVE
  This study was designed to investigate whether leptin modifies angiotensin (Ang) II-induced proliferation of aortic vascular smooth muscle cells (VSMCs) from 10-week-old male Wistar and spontaneously hypertensive rats (SHR), and the possible role of nitric oxide (NO).
  
  
  METHODS
  NO and NO synthase (NOS) activity were assessed by the Griess and (3)H-arginine/citrulline conversion assays, respectively. Inducible NOS (iNOS) and NADPH oxidase subutnit Nox2 expression was determined by Western-blot. The proliferative responses to Ang II were evaluated through enzymatic methods.
  
  
  RESULTS
  Leptin inhibited the Ang II-induced proliferative response of VSMCs from control rats. This inhibitory effect of leptin was abolished by NOS inhibitor, NMMA, and iNOS selective inhibitor, L-NIL, and was not observed in leptin receptor-deficient fa/fa rats. SHR showed increased serum leptin concentrations and lipid peroxidation. Despite a similar leptin-induced iNOS up-regulation, VSMCs from SHR showed an impaired NOS activity and NO production induced by leptin, and an increased basal Nox2 expression. The inhibitory effect of leptin on Ang II-induced VSMC proliferation was attenuated.
  
  
  CONCLUSIONS
  Leptin blocks the proliferative response to Ang II through NO-dependent mechanisms. The attenuation of this inhibitory effect of leptin in spontaneous hypertension appears to be due to a reduced NO bioavailability in VSMCs.
authors.affiliation: Metabolic Research Laboratory, University of Navarra, 31008 Pamplona, Spain. arodmur@unav.es
authors.forename: Amaia
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Javier
authors.initials: J
authors.lastname: Gómez-Ambrosi
authors.forename: Victoria
authors.initials: V
authors.lastname: Catalán
authors.forename: Ana
authors.initials: A
authors.lastname: Fortuño
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D011924:Rats, Zucker; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D001786:Blood Glucose; D020738:Leptin; D050796:STAT3 Transcription Factor; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D051057:Proto-Oncogene Proteins c-akt