title: Transient downregulation of glomerular atrial natriuretic factor receptors in high output heart failure in the rat.
abstract: OBJECTIVE
  The renal response to exogenous atrial natriuretic factor (ANF) is blunted in chronic heart failure. The aim of the present studies was to investigate whether renal ANF receptor regulation in chronic heart failure is a time related event.
  
  
  METHODS
  Glomerular ANF receptors were analysed in radioligand binding experiments at 0, 1, 2, 6, 12, 24, and 48 h, as well as at 1, 2, 4, and 8 weeks after the induction of an aortocaval shunt.
  
  
  RESULTS
  Rats with aortocaval shunts had lower packed cell volume and body weight and higher relative heart weight than sham operated controls. Plasma ANF C and N terminal levels were increased in shunt rats as early as 5 min after establishment of the shunt. Right and left atrial ANF concentrations were decreased and ventricular ANF concentration was increased in shunt rats at 6 and 12 h respectively. Competitive inhibition of 125I-ANF binding showed that at 6 h the density (Bmax) of glomerular ANF receptors was significantly lower than in the controls [518(SEM 10) v 759(12) fmol.mg-1 protein] without differences in their affinity (Kd). The low Bmax in shunt animals persisted at 12, 24, and 48 h, even at 1 week [Bmax: 400(29) and 713(28) fmol.mg-1 protein; Kd: 80(2) and 70(4) pM, for AC rats and controls, respectively]. Bmax values were not significantly different at 2, 4, and 8 weeks. In 24 h animals, C-ANF displaced 65% of total binding, with both total and C ANF binding sites being 38% lower in shunt animals.
  
  
  CONCLUSIONS
  Downregulation of glomerular ANF receptors is a transient event during the development of high output heart failure in the rat. Thus the blunted renal response to ANF during chronic heart failure is not likely to be due to a decrease in renal ANF receptor density or affinity.
authors.affiliation: Laboratory of Experimental Hypertension and Vasoactive Peptides, Clinical Research Institute of Montreal, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Gauquelin
authors.forename: M C
authors.initials: MC
authors.lastname: Bonhomme
authors.forename: R
authors.initials: R
authors.lastname: Garcia
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D006333:Heart Failure / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D013997:Time Factors
chemical_list: C472610:atrial natriuretic peptide, rat; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor