title: Downregulation of natriuretic peptide C-receptor protein in the hypertrophied ventricle of the aortovenocaval fistula rat.
abstract: OBJECTIVE
  This study examined the expression of the C-type receptor for the natriuretic peptide family (NPR-C) in the ventricles of normal and aortovenocaval (AV)-fistula rats, the latter a model of cardiac volume overload producing hypertrophy of both ventricles.
  
  
  METHODS
  Western blotting with a rabbit anti-NPR-C antibody was used to quantify NPR-C levels in ventricular membranes. NPR-C expression was localised anatomically and measured in frozen sections of cardiac tissue by histochemistry and in vitro autoradiography.
  
  
  RESULTS
  Western blot analysis revealed a single band (approximately 120 kDa) in ventricular membranes which was reduced to approximately 60 kDa after treatment with beta-mercaptoethanol. NPR-C immunoreactivity and [125I]rat ANP1-28 binding (displaceable by the NPR-C-specific ligand C-ANP 4-23) were localised to the endocardium. NPR-C protein levels, as measured by all three techniques, were reduced significantly in the hypertrophied ventricles of AV-fistula rats compared to sham-operated animals.
  
  
  CONCLUSIONS
  Volume-induced cardiac hypertrophy in the AV-fistula rat is associated with downregulation of endocardial NPR-C. This may be one mechanism by which the endocardium regulates the myocardial response to changes in haemodynamic load.
authors.affiliation: Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
authors.forename: L A
authors.initials: LA
authors.lastname: Brown
authors.forename: R A
authors.initials: RA
authors.lastname: Rutherford
authors.forename: D J
authors.initials: DJ
authors.lastname: Nunez
authors.forename: J
authors.initials: J
authors.lastname: Wharton
authors.forename: D G
authors.initials: DG
authors.lastname: Lowe
authors.forename: M R
authors.initials: MR
authors.lastname: Wilkins
mesh_terms: D000818:Animals; D001164:Arteriovenous Fistula / Q000150:complications / Q000378:metabolism*; D001345:Autoradiography; D015153:Blotting, Western; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism*; D015536:Down-Regulation; D006162:Guanylate Cyclase / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*
chemical_list: D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C