Renal interstitial hydrostatic pressure and sodium excretion during acute volume expansion in diabetic rats

Experiments were performed to test the hypothesis that the renal interstitial hydrostatic pressure (RIHP) response to acute volume expansion is suppressed in diabetes mellitus. Sprague-Dawley rats received streptozotocin (STZ rats; 65 mg/kg ip) or vehicle (Sham rats). Two weeks later, RIHP and Na(+) excretion responses to acute graded volume expansion with isotonic saline were quantified under Inactin anesthesia (0.1 mg/kg ip). In Sham rats, acute graded volume expansion to 10% body wt produced increases in RIHP (Delta = 12.2 +/- 2.4 mmHg), urine flow (Delta = 54 +/- 8 microliter. min(-1). g(-1)), and Na(+) excretion (Delta = 11.5 +/- 1.9 mueq. min(-1). g(-1)). In STZ rats, these volume expansion-induced responses were significantly blunted (RIHP by 50%, urine flow by 81%, and Na(+) excretion by 76%). Renal decapsulation eliminated the differences between STZ and Sham rats with regard to volume expansion-induced increases in RIHP, urine flow, and Na(+) excretion. Renal denervation normalized the RIHP response to volume expansion and improved the diuretic and natriuretic responses in STZ rats. Moreover, diuretic and natriuretic responses to direct changes in RIHP (induced by renal interstitial volume expansion) were blunted in STZ rats. We conclude that diminished alterations in RIHP, as well as a reduced impact of RIHP on Na(+) excretion, contribute to the impaired diuretic and natriuretic responses to acute volume expansion during the early stage of diabetes.     

Renal excretion of calcium and sodium in acute nephritis

Hypocalciuria was found in the early stages of illness in six patients aged 12 to 30 with acute nephritis. The hypocalciuria does not appear to be due to hypocalcaemia, lowered glomerular filtration rate, or hypoparathyroidism. It is suggested that the hypocalciuria is due in part to decreased intestinal absorption of calcium, though possibly there is also a primary alteration in renal tubular handling of calcium.     

Renal reflexes in the regulation of blood pressure and sodium excretion

The rich innervation of the kidney is distributed to all structures of renal parenchyma thus providing important anatomical support to the functional evidence that the renal nerves can control kidney functions and send signals on the kidney environment to the central nervous system. Efferent renal nerve fibres are known to influence renal haemodynamics by modifying arteriolar vascular tone, renin release by a direct action on juxtaglomerular cells, and the excretion of sodium and water by changing tubular reabsorption of sodium and water at the different tubular levels. Mechano- and chemo-receptors have been shown in the kidney. Afferent fibres connected with renal receptors convey signals to the central nervous system both at spinal and supraspinal levels. The central areas receiving inputs from the kidney are those involved in the control of cardiovascular homeostasis and fluid balance. Activation of renal receptors by the electrical stimulation of renal afferent fibres were found to elicit both excitatory and inhibitory sympathetic responses. Although the existence of excitatory renorenal reflexes has been suggested, electrophysiological and functional data demonstrate that neural renorenal reflexes exert a tonic inhibitory influence on the tubular sodium and water reabsorption and on the secretion of renin from the juxtaglomerular cells.     

Influence of volume expansion on sodium excretion during parabiotic dialysis.

Dialysis of a saline-infused against a noninfused dog was associated with a significant increase in Na excretion in both animals without a significant change in creatinine clearance or filtered Na. This indicates that there was movement by diffusion of a humoral agent between the two animals. The observed increase in Na excretion in the noninfused animal resulted from gain of a natriuretic hormone, since in a second series of experiments a natriuretic rather than antinatriuretic hormone appeared to be involved.     

Renal sodium transporter/channel expression and sodium excretion in P2Y2 receptor knockout mice fed a high-NaCl diet with/without aldosterone infusion

The P2Y(2) receptor (P2Y2-R) antagonizes sodium reabsorption in the kidney. Apart from its effect in distal nephron, hypothetically, P2Y(2)-R may modulate activity/abundances of sodium transporters/channel subunits along the nephron via antagonism of aldosterone or vasopressin or interaction with mediators such as nitric oxide (NO), and prostaglandin E(2) (PGE(2)) or oxidative stress (OS). To determine the extent of the regulatory role of P2Y(2)-R in renal sodium reabsorption, in study 1, we fed P2Y(2)-R knockout (KO; n = 5) and wild-type (WT; n = 5) mice a high (3.15%)-sodium diet (HSD) for 14 days. Western blotting revealed significantly higher protein abundances for cortical and medullary bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), medullary α-1-subunit of Na-K-ATPase, and medullary α-subunit of the epithelial sodium channel (ENaC) in KO vs. WT mice. Molecular analysis of urine showed increased excretion of nitrates plus nitrites (NOx), PGE(2), and 8-isoprostane in the KO, relative to WT mice, supporting a putative role for these molecules in determining alterations of proteins involved in sodium transport along the nephron. To determine whether genotype differences in response to aldosterone might have played a role in these differences due to HSD, in study 2 aldosterone levels were clamped (by osmotic minipump infusion). Clamping aldosterone (with HSD) led to significantly impaired natriuresis with elevated Na/H exchanger isoform 3 in the cortex, and NKCC2 in the medulla, and modest but significantly lower levels of NKCC2, and α- and β-ENaC in the cortex of KO vs. WT mice. This was associated with significantly reduced urinary NOx in the KO, although PGE(2) and 8-isoprostane remained significantly elevated vs. WT mice. Taken together, our results suggest that P2Y(2)-R is an important regulator of sodium transporters along the nephron. Pre- or postreceptor differences in the response to aldosterone, perhaps mediated via prostaglandins or changes in NOS activity or OS, likely play a role.     

Renal aluminum excretion

Urinary aluminum (Al) excretion was studied in humans with normal and impaired renal function. Al was measured by atomic absorption spectrometry. In healthy volunteers (n=50), renal Al excretion was 12.2±8.5 μg/24 h. Two patients on plasma exchange therapy with normal renal function and an inadvertent load of 870 and 388 μg Al/treatment showed a 23 and 14% positive balance until next treatment.     

Changes in sodium and potassium excretion and urinary volume in rats submitted to hypervitaminosis A

Hypervitaminosis A induces the following changes in rat kidney: decrease in sodium and potassium excretion and an increase of urinary volume. In order to determine the possible reversibility of these alterations, the authors allowed the hypervitaminotic animal to recover for 30 and 60 days. After a 30-day recovery period for urinary volume, a 20-day recovery period for sodium excretion, and a 10-day recovery period for potassium excretion, the alterations were reverted to normal.     

Atrial natriuretic peptide--cyclic GMP coupling and urinary sodium excretion during acute volume expansion in man

The present study examines hormonal and renal responses to acute volume expansion in normal man, with particular emphasis on the atrial natriuretic peptide (ANP)--cyclic GMP coupling. Two liters of isotonic saline were infused into eight normotensive male subjects over a 1-h period. Plasma and urinary measurements were made before, during, and up to 300 min after the start of the saline infusion. With the initial increase in urinary sodium excretion there were increases in plasma ANP and plasma cyclic GMP, which reached maximum levels at 15 min after the end of the saline infusion. Urinary cyclic GMP increased gradually during saline infusion up to approximately 60 min after the end of the infusion. Plasma ANP and plasma and urinary cyclic GMP excretion gradually declined thereafter. By contrast, urinary sodium excretion remained elevated up to the end of the observation period. The saline infusion was associated with marked reductions in plasma renin activity and aldosterone, which persisted up to the end of the study. These results suggest a coupling between the increases in plasma ANP, the production of cyclic GMP, and urinary sodium excretion, in particular during the initial renal response to acute volume expansion. However, other mechanisms including the suppression of the renin--angiotensin--aldosterone system may become increasingly important in the later natriuretic response to acute volume expansion.     

Renal amino acid excretion and aging

The urinary excretion and serum concentration of amino acids were studied in 62 healthy individuals aged 15 to 70 years. In elderly subjects (61-70 years), it was found that renal amino acid clearance per 100 ml GFR (fractional excretion, FE) rose significantly in the following amino acids: CYS, VAL, MET, ILE and LEU. Since the serum concentrations of these amino acids showed no significant changes, but the GFR was reduced, it can be concluded that the raised FE of these amino acids was due to a decrease in their effective tubular reabsorption. A significant correlation was found between FENa and FE of most amino acids including those mentioned above. The findings support the assumption that changes in tubular Na+ transport probably participate in the changes of tubular amino acid transport in elderly individuals.     

Endothelin B receptor antagonism in the rat renal medulla reduces urine flow rate and sodium excretion

It is well established that activation of endothelin B (ETB) receptor induces natriuresis and diuresis and thus reduces blood pressure. However, the site of action of ETB receptor is debatable. The present study was undertaken to address the role of renal medullary ETB receptor in renal excretory function. In volume-expanded Sprague-Dawley rats, infusion of the ETB antagonist A192621 at 0.5 mg/kg/hr to the renal medulla induced an immediate and significant reduction of urine flow rate that was 87.5% +/- 7.1%, 68% +/- 20%, and 58.3% +/- 15.5% of the control value at 10, 30, and 60 mins, respectively (n=5, P < 0.05 at each time point). Following intramedullary infusion of A192621, urinary sodium excretion remained unchanged during the first 20 mins but started to decline thereafter with a maximal effect at 60 mins. Changes in urinary excretion of potassium and chloride followed the same pattern of changes as for urinary sodium. In contrast, urinary osmolality gradually and significantly increased (control: 419 +/- 66; A192621 at 60 mins: 637 +/- 204 mOsm/kg H2O, P < 0.05). Over a 60-min period of intramedullary infusion of A192621, none of the hemodynamic parameters examined, including mean arterial pressure, renal blood flow, or medullary blood flow, were affected. These data suggest that: (i) intramedullary blockade of ETB receptor produces antidiuresis and antinatriuresis independently of hemodynamic changes, and (ii) the immediate response to intramedullary blockade of ETB receptor is the reduction of water excretion followed by the reduction of sodium excretion.