Regulation of atrial natriuretic peptide receptors in glomeruli during chronic salt loading

Regulation of atrial natriuretic peptide receptors in glomeruli during chronic salt loading. 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 ± 2mm 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°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 < 0.02), while C-receptor affinity was increased (Kd: 12 ± 3pM in NaCl-rats vs. 22 ± 5pM in C; P < 0.02). Binding sites of B-receptors did not significantly change with high sodium intake (211 ± 16 in NaCl-rats vs. 244 ± 21 fmol/mg protein), but B-receptor affinity was moderately reduced (Kd: 529 ± 27 in NaCl-rats vs. 437 ± 14 pM in C; P < 0.02). Thus, the decrease in total ANP receptors after salt loading was exclusively due to a decrease in C-receptors. During chronic high sodium intake, down-regulation of C-receptors for ANP may indirectly enhance ANP-binding to biologically active B-receptors for ANP within the rat kidney to promote sodium excretion in the absence of augmented circulating ANP