Proximal tubular transport and urinary excretion of sodium after renal denervation in sodium depleted rats

The effect of unilateral renal denervation on renal handling of water, sodium and potassium was studied with clearance and micropuncture techniques in sodium depleted anaesthetized rats in the nondiuretic state. In clearance experiments renal denervation resulted in a +140 and +320% increase in urine flow and potassium excretion, but sodium excretion of innervated (I) and denervated (D) kidneys was similar (I: 12.0±2.0, D: 14.0±3.6 nM·min^–1·g^–1; NS). However, upon the loop diuretic furosemide (1 mg·kg^–1), a marked denervation natriuresis was observed (I: 2.8±0.9, D: 5.9±1.0 M·min^–1;P<0.05) and denervation diuresis and kaliuresis persisted, too (+95 and +60%, respectively). Micropuncture results revealed that fractional reabsorption of filtrate to late proximal puncture site was depressed by renal denervation from 62 to 49% while no change in time control rats was seen (64±2 vs. 64±1%; NS). In micropuncture experiments besides augmented urine flow (+82%) from D kidneys also a small denervation natriuresis was present (I: 21.6±6.4, D: 29.2±7.0 nM·min^–1;P<0.05). It is concluded that the lack or marked attenuation of denervation natriuresis in sodium depleted rats were the result of an almost complete compensatory distal reabsorption of the excess sodium (but not of water and potassium) leaving the proximal tubule after denervation. The distal adaptive response can be overcome by furosemide.     

Urinary sodium excretion in renal stone formers

Summary In the present investigation 238 randomly selected male individuals of the general population (age 19–41 years) and 42 age-matched male patients with recurrent renal stone formation (calcium oxalate and/or calcium phosphate) were studied under outpatient conditions without dietary restrictions. Urinary Na excretion was 207 ± 82 mmol/24 h (range 55–570) in controls and 208 ± 100 (range 76–575) in recurrent renal stone formers. Both in controls (r=0.36;p < 0.01) and in stone formers (r=0.4;p < 0.01) a significant correlation was observed between urinary excretion of sodium and calcium.Urinary sodium excretion was unrelated to systolic or diastolic blood pressure in normotensive or hypertensive individuals. This finding indicates that factors other than sodium are involved in the maintenance of hypertension. Urinary sodium, presumably an index of intake of nutrients, was significantly correlated to several coronary risk factors, e.g. fasting glucose, cholesterol and overweight. There existed a significant inverse relationship between fasting plasma phosphate and urinary sodium, but not between fasting plasma phosphate and serum iPTH or urinary cAMP. This finding points to some function of sodium excretion as one determinant of plasma phosphate.

---

Abbreviations UV_Ca rate of urinary calcium excretion (mmol/24 h) - UV_Na rate of urinary sodium excretion (mmol/24 h) - TMP/GFR tubular threshold for phosphate (mg/dl) - C_Cr endogenous creatinine clearance (ml/min × 1.73 m²) - 25(OH)D serum level of 25-hydroxy-vitamin D - ECV extracellar fluid volume     

Effect of chronic preoptic lesions on the renal excretion of sodium in rats.

Rats with bilateral lesions in the preoptic area showed a normal pattern of urineand electrolyte excretion under resting conditions but complete absence of a natriuretic response to unilateral carotid baroreceptor stimulation and also a significant reduction in the rate of sodium excretion after saline loading and after a high-sodium intake. Measurements of renal clearance did not show any significant differences in glomerular filtration rate, renal plasma flow, or filtration fraction between normal and preoptic-lesion rats. Apart from the test situations used above, rats with preoptic lesions were apparently able to regulate their sodium metabolism normally because after 3 wk on a high-sodium intake their plasma and extracellular fluid volumes, plasma electrolytes, osmolaity, and mean arterial pressures were indistinguishable from normal rats.It is suggested that the preoptic component of the baroreceptor reflex pathway mighthave an input into a hypothalamic area controlling sodium excretion.     

Lipopolysaccharide reduces sodium intake and sodium excretion in dehydrated rats

The objective of this study was to find out if lipopolysaccharide (LPS) administered intraperitoneally affects sodium and water intake and renal excretion in dehydrated rats. LPS (0.3-5 mg/kg b.w.) inhibited 0.3 M NaCl intake induced by subcutaneous injection of the diuretic furosemide (FURO, 10 mg/kg b.w.) combined with the angiotensin converting enzyme inhibitor, captopril (CAP, 5 mg/kg b.w.). Only the highest doses of LPS (2.5 and 5 mg/kg) inhibited water intake induced by FURO/CAP. LPS (0.6 mg/kg) reduced urinary volume and sodium excretion, but had no effect on mean arterial pressure or heart rate of rats treated with FURO/CAP. LPS (0.3-5.0 mg/kg) abolished intracellular thirst and reduced by 50% the urine sodium concentration of rats that received 2 ml of 2 M NaCl by gavage. LPS (0.3-5.0 mg/kg) also reduced thirst in rats treated with FURO alone (10 mg/rat sc). The results suggest that LPS has a preferential, but not exclusive, inhibitory effect on sodium intake and on intracellular thirst. The inhibition of hydro-mineral intake and the antinatriuresis caused by LPS in dehydrated rats may contribute to the multiple effects of the endotoxin on fluid and electrolyte balance and be part of the strategy to cope with infections.     

Right atrium and renal sodium excretion.

Inflation of a balloon in the right atrium of 13 dogs resulted in salt and water retention not attributable to changes in GFR, RPF, filtration fraction, mean arterial pressure, left atrial pressure, or renal venous pressure. The response to right atrial balloon inflation was compared with the renal effects of constriction of the abdominal aorta above the renal arteries and constriction of the ascending aorta. Neither procedure evoked the same response as balloon inflation. Results suggest that the decrease in mean arterial pressure which accompanies balloon inflation accounts for only part of the decreased salt and water excretion. There was no significant difference between the responses of denervated and intact kidneys to right atrial balloon inflation. A binary response to stretching of the right atrium is suggested, both components apparently involving hormonal mediation.     

Effects of dopamine blockade on renal sodium excretion

The renal responses to a specific dopamine antagonist (cis-flupentixol) and its stereoisomer (trans-flupentixol), a weak dopamine antagonist, were examined during hydropenia and Ringer loading in anesthetized rats. During hydropenia glomerular filtration (GFR), absolute (UNaV), and fractional (FENa) sodium excretion rates were similar as were single-nephron filtration (SNGFR) and proximal tubular flow rate (VTF). After Ringer loading GFR, UNaV, and FENa increased in all groups, but the increments were less in the cis-flupentixol than in the control or trans-flupentixol group. SNGFR and VTF increased similarly in all groups. In another series of experiments Ringer loading was performed prior to drug administration. Perfusion pressure (PP) was decreased in trans-flupentixol rats by aortic constriction to control for cis-flupentixol-induced reduction in PP. UNAV and FENa were lower in the cis-flupentixol- than trans-flupentixol-treated rats at comparable PP and GFR. In conclusion, dopamine blockade attenuated the natriuresis of Ringer loading; the mechanism is uncertain but may be related to a tubular effect at a site beyond the proximal convoluted tubule and/or in deeper nephrons.     

The effects of P2X receptor agonists on renal sodium and water excretion in anaesthetized rats

Aim: To investigate in vivo effects of P2X receptor activation on sodium and water excretion in urine. Methods: The clearance experiments were carried out in anaesthetized rats during intravenous infusion (2 μmol kg^?1 + 20 nmol (kg min)^?1, v = 40 μL min^?1) of P2X receptors agonists: α,β‐methylene ATP (α,β‐meATP) and β,γ‐methylene ATP (β,γ‐meATP). Cortical blood flow (CBF) was estimated by laser Doppler flux during intrarenal artery infusion of β,γ‐meATP (20 nmol (kg min)^?1, v = 2 μL min^?1). Influence of α,β‐meATP and β,γ‐meATP on the activity of Na‐K‐ATPase was investigated in isolated proximal tubules. Results: Intravenous infusion of β,γ‐meATP resulted in a marked, progressively increasing diuresis and this effect was accompanied by a progressive increase in the sodium excretion rate. The glomerular filtration rate was unaffected. The effects of β,γ‐meATP were abolished by P2 receptor antagonist PPADS (70 nmol (kg min)^?1). CBF increased by 16 ± 2% during renal artery infusion of β,γ‐meATP. Furthermore, α,β‐meATP and β,γ‐meATP increased 1.5‐fold lithium clearance (C_Li). Sodium excretion, expressed as a fraction of the distal delivery (C_NaC_Li^?1), increased 1.5‐fold during infusion of α,β‐meATP or β,γ‐meATP. Both agonists at 10^?6 m produced a statistical significant decrement in the ouabain‐sensitive ATPase activity about 16–20% and these effects were blocked in the presence of PPADS. Conclusion: Activation of P2X receptors increased renal sodium and water excretion. Mechanistically, P2X agonists increased renal perfusion and inhibited sodium reabsorption via an Na‐K‐ATPase‐dependent mechanism.     

A central osmosensitive receptor for renal sodium excretion.

1. The effect on renal Na and water excretion of increasing the NaCl concentration of blood supplying the brain was investigated in conscious water-loaded sheep. Intracarotid infusion ot 4 M-NACl at 0-8 ml./min for 60 min was compared with equivalent intrajugular infusion. 2. A more rapid increase in renal Na excretion and urine osmolality occurred with the intracarotid infusions than with intrajugular infusions. 3. Intracarotid infusions of 2 M sucrose or fructose at 1-6 ml./min for greater increase in renal Na excretion, urine osmolality and a decrease in urine flow rate. 4. The results suggest that there are receptors in the brain sensitive to changes in extracellular tonicity which influence renal Na excretion. It is possible that changes in ADH secretion alone mediate the early natriuresis seen with intracarotid hypertonic infusions although an alternative concurrent mechanism cannot be ruled out.     

Effects of plasmapheresis on renal hemodynamics and sodium excretion in dogs

Summary Acute plasmapheresis in dogs reduces plasma protein concentration, without significantly altering plasma volume, glomerular filtration rate and plasma sodium concentration.The effects of acute hypoproteinemia on renal circulation is variable. In some cases, the renal plasma flow is not modified, while in others it is markedly decreased, leading to a rise in filtration fraction. The hemodynamic changes are observed in experiments inducing marked protein depletion.Acute hypoproteinemia increases sodium excretion exclusively in experiments where plasmapheresis has not reduced kidney irrigation.The lack of plasma volume expansion in the natriuretic animals cancels the necessity of postulating the secretion of some unknown natriuretic hormone to explain the decreased tubular reabsorption of sodium. The explanation of saline diuresis should be sought within the kidney itself, and the fall in peritubular oncotic pressure, occurring after plasmapheresis or during massive saline loading, offers an alternative explanation, which appears simpler and more rational.     

Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium

The effects of dietary sodium intake on the renal excretion of urodilatin and of sodium were examined in six healthy male subjects. The 24-day study period was divided into three phases of 8 days each. Subjects Ingested 2.8 mequiv sodium (kg body weight)^–1 day^–1 during the first phase, 5.6 mequiv (kg body weight)^–1 day^–1 during the second phase, and 8.4 mequiv (kg body weight)^–1 day^–1 during the third phase. The excretion of both sodium (P<0.002) and urodilatin (P<0.006) increased in response to the increasing dietary sodium, while urine flow did not change. Urinary urodilatin excretion correlated closely with renal sodium excretion (P<0.001). Serum aldosterone levels (P<0.01) as well as serum renin levels (P<0.05) significantly decreased with increasing sodium intake. Plasma [Arg]vasopressin levels increased significantly (P<0.05). Plasma atrial natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were unaltered by the changes in sodium intake. We conclude from these results that the renal natriuretic peptide, urodilatin, but not the main cardiac member of the natriuretic peptide family may be involved in the regulation of day-to-day sodium balance.     

Sympathetic modulation of renal hemodynamics,renin release and sodium excretion

Summary In anesthetized animals it has been shown previously, that the influence of electrical stimulation of efferent renal nerves on renal function with increasing stimulation frequencies can be graded; renin release is affected at low, sodium excretion at intermediate and vascular resistance at high stimulation frequencies.Experiments in conscious dogs are reviewed, which present evidence for a similar functional dissociation under physiological conditions.Moderate activations of the renal sympathetic nerves, which do not change renal blood flow 1) decrease sodium excretion independent of changes in angiotensin II, 2) interact with the pressure-dependent mechanism of renin release by resetting its threshold pressure and 3) modulate autoregulation by increasing the lower limits of glomerular filtration rate and renal blood flow-autoregulation.These findings may contribute to our understanding of the role of the renal nerves in the pathophysiology of congestive heart failure and hypertension.