Acute volume expansion and salt-loading studies in rats. The role of atrial natriuretic peptide and catecholamines.

Differences have been postulated for the mechanism of natriuresis due to atrial natriuretic peptide (ANP), salt loading with high salt diet (HS) and acute volume expansion (AcVE), in particular between AcVE and ANP based on the observed synergism between the two. Therefore the effects of and the interaction between the three were investigated in rats. ANP and AcVE produced the same natriuresis in HS as in normal salt (NS) rats and, in both, the actions of ANP and AcVe were significantly additive showing similarity in mechanisms. Synergism [(AcVE + ANP) - AcVE] was, however, present only in the NS rats. Proximal tubular sodium transport was the same with AcVE and ANP+AcVE suggesting that synergism is a property of more distal nephron segments. In conscious HS rats, plasma ANP was significantly less but natriuresis was higher than in NS rats. ANP therefore probably has some causative role in the natriuresis of AcVE but none in that of HS loading. Urinary dopamine was significantly increased by HS and further increased by AcVE in both NS and HS rats, the relationship between dopamine and natriuresis being significantly positive (r2 = 0.328) reaching equivalent levels in both NS and HS rats. Systemic benserazide prevented the increase in urinary dopamine but only attenuated the natriuresis of AcVE. We conclude that HS does not potentiate the natriuresis of AcVE or ANP, synergism between AcVE and ANP is not a proximal tubule event and dopamine accounts for significant natriuresis of VE in addition to other natriuretic factors.

Chronic volume expansion in the rat: proximal tubular Na+ transport and Na+ pump inhibition.

1. The lesser natriuresis of chronic volume expansion (ChVE) compared with that of acute volume expansion (AcVE) implies different homeostatic mechanisms. Because little information is available in the literature on proximal tubular (PT) Na+ transport and intracellular electrolyte concentrations, these were investigated in a rat model of ChVE. 2. Haematocrit was significantly lower and urine volume and Na+ excretion were significantly higher in ChVE rats compared with control rats. 3. Proximal tubular Na+ transport with artificial PT fluid was normal (3.67 +/- 0.09 x 10(-4) mm3 mm-2 s-1; mean+/-S.E.M.), while with endogenously harvested tubular fluid it was reduced to 2.78 +/- 0.07 x 10(-4) mm3 mm-2 s-1 in ChVE rats (P < 0.0001). 4. Intracellular Na+ was significantly elevated from 18.0 +/- 0.7 mmol (kg wet wt)-1 in control rats to 20.2 +/- 0.8 mmol (kg wet wt)-1 in ChVE rats (P = 0.044). The cells showed residual swelling, with dry weight and phosphorus values decreasing significantly compared with controls (19.5 +/- 0.4 to 18.5 +/- 0.03% and 130.4 +/- 3.7 to 117.8 +/- 2.8 mmol (kg wet wt)-1, P = 0.04 and 0.006, respectively). 5. The results demonstrate that in ChVE a tubular factor inhibits PT Na+ transport associated with an inhibition of the Na+ pump and this resembles one mechanism defined in AcVE.

Proximal tubular cell electrolytes during volume expansion in the rat.

1. Proximal tubular intracellular elements were measured by electron microprobe X-ray analysis (a) in rats volume-expanded with albumin-saline in which peritubular oncotic pressure remained normal and (b) in rats in which the renal artery was snared before volume expansion (the early snare model). Glomerular filtration rate and urine Na+ excretion were measured in addition to intracellular Rb+ following a 30 s infusion of RbCl as a marker for K+ transport. 2. In albumin-saline volume-expanded rats, intracellular levels of Na+ ([Na+]i) at 21.5 +/- 0.6 mmol (kg wet wt)-1, Cl- ([Cl-]i) at 18.0 +/- 0.4 mmol (kg wet wt)-1 and Rb+ ([Rb+]i) at 9.4 +/- 0.4 mmol (kg wet wt)-1 were significantly higher (P < 0.0001) than the levels in non-expanded rats ([Na+]i, [Cl-]i and [Rb+]i at 17.7 +/- 0.4, 14.6 +/- 0.3 and 4.7 +/- 0.4 mmol (kg wet wt)-1, respectively; means +/- S.E.M.). The data are consistent with Na+ pump inhibition in the proximal tubule, although this cannot be directly derived from intracellular element measurements. 3. In an early snare model of volume expansion, [Na+]i, intracellular K+ ([K+]i) and [Rb+]i remained unchanged (16.1 +/- 0.4, 131.0 +/- 2.0 and 5.2 +/- 0.3 mmol (kg wet wt)-1, respectively) compared to non-expanded snared kidneys (15.9 +/- 0.6, 131.3 +/- 1.8 and 4.8 +/- 0.3 mmol (kg wet wt)-1, respectively). [Cl-]i at 18.3 +/- 0.5 mmol (kg wet wt)-1 increased (P < 0.0008) compared to controls at 15.8 +/- 0.5 mmol (kg wet wt)-1. Thus, in these rats, evidence for an inhibition of the Na+ pump was no longer observed. This points to a major intrinsic mechanism within the kidney for mediating natriuresis, since circulating factors were identical to those in the unsnared kidney, where significant natriuresis occurred.

Effect of atrial natriuretic peptide on cellular element concentrations in rat proximal tubules: evidence for inhibition of the sodium pump.

1. In order to further define the action of atrial natriuretic peptide (ANP) on proximal tubular (PT) transport, combined clearance and electron microprobe X-ray (EMPX) experiments were performed on five male Wistar rats infused with ANP (0.16 nmol/kg per h) and nine control animals. 2. Electron microprobe X-ray analysis of PT cell electrolytes (mmol/kg wet weight) revealed a similar [Na]i in both the control and ANP treated groups (16.4 +/- 0.4 vs 16.5 +/- 0.4; P = 0.894). [Cl]i was lower in the ANP treated animals (14.8 +/- 0.3 vs 12.0 +/- 0.3; P < 0.0001) as was [K]i (131.4 +/- 1.4 vs 114 +/- 1.7; P < 0.0001). The PT cells in the ANP treated group had a significant reduction in dry weight (20.1 +/- 0.3 g% vs 19.0 +/- 0.3 g%; P < 0.024), indicating significant cell swelling. Thus, despite a normal [Na]i, there was net accumulation of Nai following ANP treatment. 3. These results are consistent with accumulation of Nai due to inhibition of the Na pump followed by cell swelling and subsequent regulatory volume decrease with exit of K and Cl. These results are the first to show the effect of ANP on PT intracellular electrolytes.

Differential effects of angiotensin II and noradrenaline on tubular rejection of sodium produced by ANP in rats.

The effect of Atrial Natriuretic Peptide (ANP) on renal tubular sodium handling (FENa) in the presence of converting enzyme inhibition (CEI), the AII antagonist Saralasin (SAR), noradrenaline (NA) and angiotensin II (AII) infusions was investigated. FENa and increases in FENa produced by ANP were significantly lower with CEI (p less than 0.03 and 0.0001) or SAR (p less than 0.02 and 0.02) against control (Vehicle + ANP). Mean arterial pressures (MAP) were also reduced. Returning MAP to 107 +/- 2 mmHg with NA (+CEI+ANP), did not change FENa (1.22% +/- 0.16 to 1.25% +/- 0.18, p greater than 0.66) whereas without CEI but with ANP (MAP 113 +/- 2 mmHg) FENa was significantly increased by NA (2.34% +/- 0.36, p less than 0.02). With AII+CEI+ANP, MAP was restored to 110 +/- 5 mmHg, and FENa was highly significantly increased (0.99% +/- 0.20 to 3.04% +/- 0.39, p less than 0.0003) in excess of that expected due to pressure effects alone. It is concluded the additional effect of AII on FENa (3.04 versus 1.25% with NA) at equivalent perfusion pressures are due to a separate additive phenomenon of AII and ANP both causing tubular rejection of Na.