Renal sympathetic nerves modulate glomerular ANP receptors and filtration

We examined characteristics of atrial natriuretic peptide (ANP) receptors in glomeruli isolated from subacutely (3-5 days) denervated (DNX) and contralateral nondenervated (non-DNX) kidneys of normal rats (NL) and rats subjected to water deprivation for 48 h (WD). Total ANP receptor density in DNX kidneys of WD rats, measured by competitive inhibition binding between ¹²⁵I-labeled ANP and ANP, was twofold higher than non-DNX kidneys (726 ± 96 vs. 384 ± 32 fmol/mg protein, P < 0.05). Equilibrium association constant (K_a) was not significantly different (2.33 ± 0.43 vs. 3.34 ± 0.78 × 10⁹ M^-1). In NL rats, there was no difference in ANP receptor density between DNX and non-DNX kidneys (244 ± 20 and 264 ± 16 fmol/mg protein). Production of guanosine 3′,5′-cyclic monophosphate (cGMP), a putative second messenger of ANP, in response to ANP (10^-7 M) in glomeruli isolated from DNX was significantly larger than non-DNX kidneys of WD rats. To determine whether these changes in ANP receptors have functional consequences in vivo, glomerular capillary ultrafiltration coefficient (K_f) was assessed by micropuncture technique in WD Munich-Wistar rats. In DNX kidneys, ANP infusion (4 μg · kg^-1 · h^-1) significantly increased whole kidney glomerular filtration rate (GFR) and single-nephron (SN) GFR (0.64 ± 0.06 to 0.89 ± 0.17 ml/ min and 25 ± 2 to 33 ± 2 nl/min, respectively; n = 7) and K_f (1.26 ± 0.29 to 2.18 ± 0.41 nl · min^-1 · mmHg^-1). In contrast, in non-DNX kidneys of WD rats, increase in GFR was significantly less (0.48 ± 0.05 to 0.59 ± 0.03 ml/min, n = 6, change P < 0.05 vs. DNX), and there were no changes in SNGFR or K_f in response to ANP. Functional studies, together with binding and cGMP production data, suggest that renal sympathetic nerves modulate glomerular filtration function by counter-regulating glomerular ANP receptors.