The effects of chronic salt loading on atrial natriuretic peptide (ANP) receptor density and affinity were studied in isolated renal glomeruli of male Sprague-Dawley rats, which received 0.9% saline as drinking fluid (NaCl-rats) and a normal rat chow diet for 35 days (N = 12). Animals on a low sodium intake received the same diet, but deionized water and served as controls (C) (N = 12). After 35 days blood pressure was only slightly increased to 136 +/- 9 in NaCl-rats versus 120 +/- 2 mm Hg in C (NS). Glomerular filtration rate, plasma cGMP and plasma ANP remained unaltered. Determination of total ANP receptor characteristics in these rats indicated a significant down-regulation of ANP receptors in salt loaded rats. Since ANP-stimulated cGMP formation was not affected by salt loading, the roles of clearance (C) and of biologically active (B) receptors were further evaluated at 21 degrees C on freshly isolated and acid washed (pH 5) glomeruli in seven animals after 35 days of salt loading and in seven animals on a low sodium intake. B-receptors were assessed by blocking C-receptors with 4-23 cANP. C-receptor numbers were lower in NaCl-rats (97 +/- 8 vs. 184 +/- 14 fmol/mg protein in C; N = 7; P less than 0.02), while C-receptor affinity was increased (Kd: 12 +/- 3 pM in NaCl-rats vs. 22 +/- 5 pM in C; P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)