Rats with aortocaval (A-V)
fistula, an experimental model of
congestive heart failure (CHF), display high circulating
atrial natriuretic peptide (
ANP) levels and a markedly blunted natriuretic response to
ANP infusion. The present study was designed to evaluate whether alterations in renal
ANP receptors may contribute to renal hyporesponsiveness to
ANP in experimental CHF. Densities (Bmax) and dissociation constants (Kd) of both the biologically active (ANPA) and clearance receptors (ANPC) were evaluated in glomerular and papillary membranes from A-V
fistula rats (n = 18) and
sham-operated controls (n = 20). ANPA and ANPC receptor subtypes were assayed by displacement of 125I-ANP-(99-126) bound to glomerular or papillary membranes by increasing concentrations of unlabeled
ANP-(99-126) or des-(18-22)-ANP-(4-23), an analogue which binds only to ANPC. Seven days after the operation, rats with A-V
fistula displayed avid
sodium retention, elevated plasma
renin activity, and approximately a 10-fold increase in plasma
ANP levels. Bmax of total
ANP binding sites was significantly decreased in rats with A-V
fistula compared with controls (220 +/- 61 vs. 399 +/- 88 fmol/mg
protein, P < 0.05). The decrease was mainly due to a reduction in ANPA receptor density (51 +/- 10 vs. 110 +/- 15 fmol/mg
protein, P < 0.05) with no change in receptor affinity. Likewise, a significant reduction in the density of ANPA (23 +/- 5 vs. 64 +/- 10 fmol/mg
protein, P < 0.05) with no change in receptor affinity was observed in papillary membranes of rats with A-V
fistula.(ABSTRACT TRUNCATED AT 250 WORDS)