title: Angiotensin II upregulation of cardiomyocyte adiponectin production is nitric oxide/cyclic GMP dependent.
abstract: BACKGROUND
  Adiponectin is a circulating cytokine that is now known to be synthesized by cardiomyocytes. Accumulating evidence has shown that adiponectin production is upregulated in patients with heart failure, with activation of the renin-angiotensin system and increased formation of angiotensin (Ang) II playing a critical role in left ventricular remodeling and heart failure. To determine whether Ang II upregulates adiponectin in hypertrophic cardiomyocytes, the authors need to explore the underlying mechanisms that could be involved.
  
  
  METHODS
  To test this hypothesis, neonatal rat ventricular myocytes (NRVMs) were treated with various concentrations of Ang II, and adiponectin expression was measured by quantitative real-time reverse transcription-polymerase chain reaction and Western immunoblotting.
  
  
  RESULTS
  Adiponectin mRNA expression was significantly increased by Ang II at concentrations from 10(-6) to 10(-8) M and was increased in a time-dependent manner at concentrations of 10(-7) M. Angiotensin type-2 receptor activation is required for Ang II-stimulated effects on adiponectin. A nitric oxide synthase inhibitor (Nx-nitro-l-arginine methyl ester hydrochloride) and an analog of cGMP antagonist (Rp-8-Br-CGMP-S) blocked Ang II-mediated upregulation of adiponectin.
  
  
  CONCLUSIONS
  These data suggest a mechanism whereby Ang II upregulates adiponectin in NRVMs via the angiotensin type-2 receptor/nitric oxide/cGMP/ protein kinase G signaling pathway.
authors.affiliation: Department of Cardiovascular Medicine, Second Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Bingyan
authors.initials: B
authors.lastname: Guo
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Han
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D052242:Adiponectin; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP