title: Down-regulation of C-type natriuretic peptide receptor by vasonatrin peptide in cardiac myocytes and fibroblasts.
abstract: OBJECTIVE
  To investigate the regulatory effects of vasonatrin peptide (VNP) on the expression of C-type natriuretic peptide receptor (NPR-C) in cultured neonatal rat cardiac myocytes and fibroblasts.
  
  
  METHODS
  Quantitative RT-PCR was undertaken to evaluate the levels of NPR-C mRNA and radioimmunoassay was used to determine the formation of intracellular cGMP.
  
  
  RESULTS
  Twenty-four hours hypoxic exposure increased the level of NPR-C mRNA in cardiomyocytes, while did not alter the expression of NPR-C in cardiac fibroblasts. VNP (10(-8)-10(-6) mol/L) reduced the levels of NPR-C mRNA in cardiac myocytes induced by hypoxia in a concentration-dependent manner, and with high concentration (10(-6) mol/L) also decreased the expression of NPR-C in cardiac fibroblasts and air-control cardiac myocytes. The inhibitory effects of VNP on the expression of NPR-C was mimicked by 8-bromo-cGMP 10(-6) mol/L (a membrane permeable analog of cGMP). VNP (10(-8)-10(-6) mol/L) increased the formation of intracellular guanosine-3',5'-cyclic monophosphate (cGMP) in both cardiac myocytes and fibroblasts. HS-142-1, the particulate guanylyl cyclase-coupled receptor antagonist, partially abrogated the above effects of VNP.
  
  
  CONCLUSIONS
  Hypoxic exposure for 24 h up-regulated the expression of NPR-C in cultured neonatal rat cardiac myocytes. VNP decreased the expression of NPR-C in cardiac myocytes and fibroblasts under both air-control and hypoxic condition, which was at least partially mediated by guanylate cyclase linked natriuretic peptide receptors through increasing the intracellular cGMP.
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi-an 710032, China.
authors.forename: Shun-yan
authors.initials: SY
authors.lastname: Lü
authors.forename: Miao-zhang
authors.initials: MZ
authors.lastname: Zhu
authors.forename: Dian-shi
authors.initials: DS
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Hai-tao
authors.initials: HT
authors.lastname: Guo
authors.forename: Yu-zhen
authors.initials: YZ
authors.lastname: Hu
authors.forename: Qi-ming
authors.initials: QM
authors.lastname: Wei
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000096:biosynthesis* / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C068986:ventricular natriuretic peptide, eel; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C; D006152:Cyclic GMP