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 (Ka) 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 (Kf) 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 Kf (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 Kf 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.
|ジャーナル||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|出版ステータス||Published - 1991|
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