HETEROGENEOUS REGULATION OF RENAL ATRIAL-NATRIURETIC-FACTOR RECEPTOR SUBTYPES IN ONE-KIDNEY, ONE CLIP HYPERTENSIVE RATS

Objectives: To investigate the regulation of papillary atrial natriure tic factor (ANF) receptors and the differential regulation of glomerul ar ANF receptor subtypes in one-kidney, one clip (1-K, 1C) hypertensio n. Methods: Plasma immunoreactive ANF levels and atrial and ventricula r ANF content were measured in 1-K, 1C rats and their normotensive uni nephrectomized controls. Glomerular and papillary ANF receptor subtype s were characterized by competitive radioligand binding assay. Stimula tion of cyclic GMP (cGMP) production, by increasing ANF doses, was exa mined in isolated glomeruli. Results: Plasma amino-terminal ANF levels were higher in 1-K, 1C than in control rats. ANF concentrations in th e left atrium were lower and ventricular ANF concentrations were highe r in the 1-K, 1C group. Competition binding curves for glomerular memb ranes revealed the presence of two binding sites (ANF-R1 and ANF-R2) i n both groups. Total glomerular ANF receptor density was lower in 1-K, 1C rats than in their normotensive controls. Both receptor subtypes w ere downregulated in 1-K, 1C rats and their relative proportion was si milar to that in glomerular preparations from the controls. ANF-stimul ated cGMP production by isolated glomeruli was lower in 1-K, 1C than i n normotensive rats. In papillary membranes, ANF was bound to a homoge neous population of high-affinity binding sites in both groups. A mode st augmentation in the density of papillary ANF receptors was observed in 1-K, 1C rats. Conclusion: Glomerular and papillary ANF receptors m ay be regulated differently in the presence of elevated plasma ANF lev els. The present results indicate that the downregulation of glomerula r ANF-R1 and the reduced cGMP response may lead to altered sodium and water handling by the kidney of 1-K, 1C hypertensive rats.