Downregulation of atrial natriuretic factor clearance receptors in
experimental chronic renal failure rats.
Luk, James K. H., Eric F. C. Wong, and Norman L. M. Wong.
Department of Medicine, University of British Columbia, Vancouver
Hospital and Health Sciences Centre, Koerner Pavilion, Vancouver, BC
Canada
APStracts 2:0132H, 1995.
Studies were performed to examine the changes of renal ANF second
messenger (cGMP) responses and receptor properties in chronic renal
failure (CRF). 5/6 nephrectomized and sham-operated Wistar rats were
used. The glomerular filtration rate (GFR) was decreased in the 5/6
nephrectomized rats, which also had significantly higher plasma BUN
and plasma ANF levels (148.5 +/- 10.2 vs 115.7 +/- 7.3 pg/ml, p=0.01)
than the sham rats. In vitro ANF-stimulated cGMP accumulations in
glomeruli of 5/6 nephrectomized rats were higher than controls.
Radioligand binding experiments showed downregulation of the total
ANF receptor in both acid and non-acid wash CRF glomeruli (non-acid
wash: 189 +/- 25 vs 362.8 +/- 52.8 fmol/mg protein, p<0.05; acid
wash: 449.8 +/- 67 vs 652.7 +/- 52.5 fmol/mg protein, p<0.05). No
change in receptor densities was observed in the dANP-resistant
receptors between sham and CRF rat glomeruli. Therefore,
downregulation of ANF clearance receptors exists in CRF rat glomeruli
and this is associated with the exaggerated ANF-stimulated cGMP
response in these CRF glomeruli. Hypersensitivity of CRF rat to ANF,
together with high plasma ANF levels and downregulation of clearance
receptor, may contribute to increased sodium excretion in CRF.
Received 22 April 1994; accepted in final form 16 March 1995.
APS Manuscript Number H357-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.