Administration of atrial natriuretic factor inhibits sodium-coupled transport in proximal tubules.

Abstract

The newly discovered peptides extracted from cardiac atria, atrial natriuretic factors (ANFs), when administered parenterally cause renal hemodynamic changes and natriuresis. The nephron sites and cellular mechanism accounting for profound increase in Na' excretion in response to ANFs are not yet clarified. In the present study we investigated whether synthetic ANF peptide alters the reabsorption of Na' and reabsorption of solutes cotransported with Na' in the proximal tubules of rats.Synthetic ANF peptide consisting of 26 amino acids, 4 ag/kg body wt/h, or vehicle in controls, was infused to surgically thyroparathyroidectomized anesthetized rats. After determination of the fractional excretion (FE) of electrolytes (Na', K+, P,, Ca2+, Mg2+, HCO3), the kidneys were removed and luminal brush border membrane vesicles (BBMVs) were prepared from renal cortex. Solute transport was measured in BBMVs by rapid filtration techniques. Infusion of ANF peptide increased FENa, FEp,, and FEHCO,; but FEc., FEK, and FEMg were not changed. The increase in FENa was significantly correlated, on the one hand, with increase of FEp, (r = 0.9, n = 7; P < 0.01) and with increase of FEHCO3 (r = 0.89, n = 7; P < 0.01). On the other hand, FEN. did not correlate with FEK, FEca, or with FEM.. The Na+ gradient-dependent uptake of Pi by BBMVs prepared from renal cortex of rats receiving ANF infusion was significantly (P < 0.05) decreased (-25%), whereas the Na+ gradient-dependent uptake of L-13H]proline and of D-I3Higlucose or the diffusional uptake of 22Na+ were not changed. ANF-elicited change in FEn showed a close inverse correlation with decrease of Na+-dependent Pi uptake by BBMVs isolated from infused rats (r = 0.99, n = 7; P < 0.001). Direct addition of ANF to BBMVs in vitro did not change the Na+ gradient-dependent Pi uptake. In rats infused with ANF, the rate of amiloride-sensitive Na+-H+ exchange across the brush border membrane (BBM) was significantly (P < 0.05) decreased (-40%), whereas the diffusional 22Na+ uptake (0.5 min) and the equilibrium (120 min) uptake of 22Na+ were not changed. The inhibition of Na+-H+ exchange after ANF was likely due to alteration of the BBM antiporter itself, in that the H+ conductance of BBMVs was not increased. We conclude that synthetic ANF (a) decreases tubular Na+ reabsorption linked to reabsorption of HCO3 in proximal tubules, and (b) inhibits proximal tubular reabsorption of Pi coupled to Na+ reabsorption, independent of secretion and/or

Modulation of the natriuretic response to atrial natriuretic peptide by alterations in peritubular Starling forces in the rat.

“…l6 - 23 It seems, howev- er, that these results were most likely a consequence of increased tubule flow rates and filtered loads, since a direct effect of ANP on volume absorption in rabbit proximal straight and convoluted tubules in vitro has not been observed. 24 In addition, micropuncture studies during ANP infusion showed increased absolute proximal and loop solute and fluid reabsorption rates with decreases only in fractional reabsorption.…”

“…23 An additional possible mode of action is the ability of ANP to act as a potent renal vasodilator, 4 ' 6 which may serve to alter peritubular capillary physical factors and thereby promote natriuresis and diuresis. Earley and coworkers 7 implicated peritubular Starling forces as important determinants of the control of sodium and water excretion, based on studies in which infusions of vasodilators, such as acetylcholine or bradykinin, led to increments in sodium and water excretion.…”

The effects of atrial natriuretic peptide on renal function and the renin-aldosterone system in anesthetized rabbits.

“…Whether atrial natriuretic peptides or atrial natriuretic factors have direct tubular effect or not is controversial. Hammond et al (1985) reported that administraiton of atrial natriuretic factor inhibits sodiumcoupled transport in proximal tubules. Burnett et al (1986) also observed that whole kidney fractional delivery of sodium from the proximal tubule as estimated by the fractional excretion of lithium was increased.…”

“…But the mechanism by which atrial extract or atrial natriuretic peptide produces a natriuresis and diuresis is still unclear. Some studies have suggested that contribution of an increase in renal blood flow (Keeler and Azzarolo 1983;Wakitani et al 1985) or glomerular filtration rate Maack et al 1984 ; Beasley and Malvin 1985;Huang et al 1985) to the natriuresis and diuresis, and others have indicated direct tubular effects (Briggs et al 1982; Sonnenberg et al 1982; Pollock and Banks 1983; Burnett et al 1984Burnett et al , 1986Hammond et al 1985).…”

Regulation of phosphate transport in proximal tubules

“…In addition to PKA and PKC pathways, regulation of the amount of NaPi-lla by a pathway that involves protein kinase G should also be considered. Early studies documented that part of the renal response to the atrial natriuretic factor (ANF) includes changes of Na + /P i cotransport [48]. Later, it was demonstrated that increases of cGMP concentrations induced by ANP or by nitric oxide (NO) resulted in a down-regulation of NaPi-lla [3].…”