Effect of renal venous pressure elevation on tubular sodium and water reabsorption in the dog kidney

This study was performed in order to quantify the effects of renal venous pressure (RVP) elevation on absolute and fractional reabsorption rates of sodium and water in proximal and distal segments of the nephron in dog kidneys. Renal blood flow (RBF) was measured electromagnetically. Clearance of [51Cr]EDTA was used as a measure of the rate of glomerular filtration (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance were used for assessing the absolute and fractional reabsorption rates of sodium and water in the proximal as well as in more distal segments of the nephron. In the kidneys with intact innervation RVP elevation to 19.9 +/- 0.1 mmHg caused significant increases in both absolute (APR) and fractional (FPR) proximal reabsorption rates from 33.4 +/- 4.2 to 38.7 +/- 2.0 ml min-1 and from 0.62 +/- 0.04 to 0.71 +/- 0.04, respectively. These responses were unaffected by acute surgical denervation of the kidneys. In contrast, chronic renal denervation or infusion of phentolamine (5 micrograms kg-1 min-1) into the renal artery eliminated the increase in APR and FPR during RVP elevation to 20 mmHg. Chronic, but not acute renal denervation depleted renal tissue content of adrenaline and noradrenaline. The results suggest that the increase in APR and FPR during RVP elevation is due mainly to local sympathetic reflex mechanisms.     

Hemodynamic and functional changes during renal venous stasis in dog kidneys

The effect of renal venous pressure (RVP) elevation on renal hemodynamics and tubular function was studied in neurolept anaesthetized dogs. Renal blood flow (RBF) was measured electromagnetically. Clearance of 51Cr-EDTA was used as a measure of the rate of glomerular filtration (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance (CLi) were used for assessing the absolute and fractional reabsorption rates of sodium and water in the proximal as well as in more distal segments of the nephron. The vasoconstrictor response to RVP elevation was partly abolished by acute surgical denervation or by local application of lidocain on the renal capsule, suggesting that RVP elevation activates an adrenergic vasoconstrictor reflex comprising the spinal cord, and elicited from stretch receptors located in the renal capsule. Further studies in alpha-adrenoceptor blocked or chronic denervated kidneys and in decapsulated kidneys favour the view, that neurogenic and myogenic mechanisms significantly influence the vasoconstrictor response to RVP elevation: The neurogenic contribution to the vasoconstrictor response comprising intrarenal and extrarenal vasoconstrictor mechanisms evoked reflexly by RVP elevation; the myogenic contribution to the vasoconstrictor response comprising opposing vasodilator mechanisms due to increase in renal interstitial tissue pressure during RVP elevation. Studies carried out in intact kidneys, acutely surgically or chronically denervated kidneys or alpha-adrenoceptor blocked kidneys indicate that the increase in proximal reabsorption rates during moderate RVP elevation is due mainly to local intrarenal alpha-adrenergic reflex mechanisms, since the decrease in CLi (during constant filtered load) induced by RVP elevation was unaffected by acute surgical denervation, but completely abolished by chronic denervation of the kidney, or by local alpha-adrenoceptor blockade of the kidney.     

Hemodynamic and excretory response of the neonatal canine kidney to acute volume expansion.

It is generally recognized that developing animals retain sodium due to an enhanced reabsorption in distal tubule segements, even when the amount administered is in excess of their needs. This study was designed to test the relationship between this relative inability to dispose of a saline load and the functional characteristics of the kidney during postnatal maturation. In addition, we explored the role played by some of the factors known to affect natriuresis in the adult subject. Measurements of sodium excretion, glomerular filtration rate (GFR), and renal blood flow (RBF) and its intrarenal distribution were made in three age groups of puppies and in adult dogs. During expansion the GFR rose rapidly and to a similar extent at all ages, but it fell thereafter, the rate of decline being much slower in adult than in developing animals (P less than 0.001). RBF and its intrarenal distribution were not altered by volume expansion. The degree of natriuresis did not reflect either the age-related or the expansion-induced changes in GFR. Fractional and absolute sodium excretion were substantially higher in 2-wk-old puppies than in either 1- or 3-wk-old animals (P less than 0.002). These findings demonstrate that the blunted renal response of the maturing animal to saline loading is due to the persistence of an enhanced tubular reabsorption rather than to a limitation in glomerular filtration.     

Oxygen requirement of bicarbonate-dependent sodium reabsorption in the dog kidney

The ratio between changes in sodium reabsorption and renal oxygen consumption (Na/O2) was measured in anesthetized dogs at high plasma bicarbonate concentration (32 +/- 1 mM); ethacrynic acid was infused continuously to prevent variations in transcellular NaCl reabsorption when sodium reabsorption was altered by varying plasma PCO2 and glomerular filtration rate (GFR). At high plasma PCO2 (110 mmHg) sodium reabsorption varied in proportion to GRF between 50 and 125% of control GFR (glomerulotubular balance). By reducing PCO2 to 20 mmHg, sodium reabsorption was reduced by 50-60% at constant GFR. The Na/O2 ratio was not significantly different during the two procedures and averaged 48 +/- 2. The ratio between changes in NaHCO3 reabsorption and oxygen consumption averaged 17 +/- 1, which is not significantly different from the Na/O2 ratio of Na-K-ATPase-dependent sodium transport. We propose that NaHCO3 is admitted to the cell by Na+/H+ exchange and that sodium is actively transported by Na-K-ATPase across the peritubular cell membrane; NaHCO3 provides the osmotic force for paracellular reabsorption of water and NaCl (bicarbonate-dependent reabsorption) without additional energy requirement.     

Red-cell lithium-sodium countertransport and renal lithium clearance in hypertension

Red-cell lithium-sodium countertransport is increased in patients with essential hypertension. It has been proposed that sodium-hydrogen ion exchange in the brush border of the renal proximal tubules is analogous to red-cell countertransport. To investigate the rate of sodium reabsorption by the proximal renal tubules in hypertension, we measured lithium clearance (a measure of proximal tubular reabsorption of sodium), as well as red-cell countertransport, in 14 patients with untreated essential hypertension and in 31 controls. As a group, the hypertensive patients had a higher average (+/- SEM) rate of red-cell countertransport (0.378 +/- 0.030 mmol of lithium per liter of cells per hour, P less than 0.01) and a lower renal fractional lithium clearance (13.96 +/- 0.69 percent, P less than 0.01) than normotensive subjects (0.317 +/- 0.015 mmol of lithium per liter of cells per hour and 17.75 +/- 0.81 percent, respectively). Within the normotensive group, subjects with hypertension in at least one first-degree relative had significantly lower fractional lithium clearances than subjects with no hypertensive relatives (15.37 +/- 0.84 percent vs. 19.06 +/- 1.07 percent, P less than 0.05). We conclude that hypertensive patients have heightened proximal tubular reabsorption of sodium and that red-cell countertransport is a marker of the renal abnormality. Enhanced proximal tubular sodium reabsorption may precede the development of essential hypertension.     

Maleic acid-induced reabsorptive dysfunction in the proximal and distal nephron

Micropuncture and clearance studies were performed to assess reabsorptive function in the proximal and distal nephron of rats with experimental Fanconi's syndrome induced by maleic acid. Anesthetized rats were studied by free-flow micropuncture of the late proximal tubule 90-120 min after continuous intravenous administration of maleic acid, 100 mg X kg-1 X h-1. Compared with control rats, the reabsorption of sodium and phosphate was significantly reduced (P less than 0.001 and less than 0.02, respectively). Tubular fluid-to-ultrafiltrate (TF/UF) chloride concentration ratio was 1.00 +/- 0.02 compared with 1.16 +/- 0.03 (P less than 0.01) in controls, suggesting a nearly total inhibition of proximal bicarbonate reabsorption. Whole kidney fractional excretions of sodium and chloride were increased significantly (P less than 0.02) but could not be explained by enhanced delivery of these solutes out of the late proximal tubule. To assess whether distal nephron reabsorption of sodium and chloride were inhibited by maleic acid, clearance studies were performed during water diuresis in awake rats. During maleic acid administration, 200 mg X kg-1 X h-1, urine flow rate (P less than 0.02) and the fractional excretions of sodium and chloride (P less than 0.001) increased significantly, but fractional free water clearance decreased from 7.16 +/- 0.42 to 4.03 +/- 0.68% (P less than 0.001). In acetazolamide-treated control rats but not in maleic acid-treated rats with similar bicarbonaturia, the magnitude of fractional free water clearance closely approximated the simultaneously measured fractional distal delivery of chloride. These studies suggest that maleic acid inhibits reabsorption at a distal nephron site or sites as well as in the proximal tubule.     

Effect of infusion of pharmacologic amounts of vasopressin on renal electrolyte excretion.

Aqueous vasopressin was infused to bicarbonate- and glucose-loaded dogs and to nonloaded antidiuretic dogs in doses of 50 mU/kg per min or 50 mU/kg per h. Both doses caused a marked increase in sodium, chloride, and water excretion. The larger dose raised the fractional excretion (sodium clearance (C-Na)/glomerular filtration rate (GFR) times 100) of these ions from 2% or less to in excess of 20%. Blocking the pressor effects of these doses of vasopressin with sodium nitroprusside did not alter the marked natriuretic and chloriuretic effect. The maximal rate of bicarbonate and glucose reabsorption was not depressed by vasopressin infusion; fractional phosphate excretion, however, was markedly increased. Inhibiting distal hydrogen ion secretion by inducing selective aldosterone deficiency failed to uncover a vasopressin-induced inhibition of proximal bicarbonate reabsorption that might have been masked by increased distal bicarbonate reabsorption. There was no significant change in GFR, renal plasma flow, or filtration fraction. The distribution of cortical renal blood flow (measured by the radioactive microsphere technique) shifted toward the inner cortex after vasopressin administration. Vasopressin, in pharmacologic doses, is a potent diuretic that most likely exerts this effect by directly inhibiting sodium reabsorption at a point in the nephron distal to the proximal tubule.     

Effect of parathyroid hormone secretion on sodium reabsorption by the proximal tubule.

To determine if an increase in the endogenous secretion of parathyroid hormone could decrease sodium reabsorption by the proximal tubule, the ionized calcium concentration of blood perfusing the parathyroid gland of eight unilaterally thyroid parathyroidectomized dogs (TPTX) was reduced by infusion of an isotonic sodium citrate plus sodium chloride solution into the blood supply of the parathyroid gland. The fractional clearance of phosphate increased significantly (+9.3 +/- 2.8 ml/min per 100 ml GFR), while fractional sodium reabsorption by the proximal tubule decreased (-.06 +/- .02; P less than .025). In seven normal control dogs that received isotonic sodium chloride infusion, neither fractional sodium reabsorption by the proximal tubule nor the fractional clearance of phosphate was significantly altered. In five bilaterally TPTX dogs that received a sodium citrate plus sodium chloride infusion, sodium reabsorption by the proximal tubule was not significantly altered. There were no significant changes in glomerular filtration rate or renal plasma flow in any of these groups. The data demonstrate that alterations in endogenous parathyroid hormone secretion can play a significant role in the regulation of sodium reabsorption by the proximal tubule.     

Neural control of renal excretory function during behavioral stress in conscious dogs

The renal and neural mechanisms underlying the excretory response to behavioral stress (aversive conditioning) were examined in 30 conscious dogs. Twenty-one dogs decreased urine flow more than 20% during stress, whereas 9 dogs showed less than a 10% decrease. In 11 of the 21 renal-reactive dogs, decreases in urine flow (42%) and sodium excretion (45%) were associated with unchanged glomerular filtration (-1.5%; GFR; inulin clearance) and effective renal blood flow (-4%; RBF; p-aminohippurate clearance). In the other 10 renal-reactive dogs, similar declines in urine flow (54%) and sodium excretion (52%) occurred with decreases in GFR (24%) and RBF (27%). Among all 30 dogs, greater increases in cardiovascular activity during stress were associated with greater decreases in renal excretion. Surgical renal denervation abolished the excretory response to stress in 4 of 5 dogs. These findings suggest that excretory responses in most dogs are mediated 1) primarily via increased tubular reabsorption rather than decreased GFR, 2) via central integration with cardiovascular responses, and 3) via the renal nerves.     

Effects of endothelin on renal haemodynamics and segmental sodium handling in conscious rats

The effects of endothelin (100 and 600 pmol/kg) on renal plasma flow (RPF), glomerular filtration rate (GFR), sodium excretion (U_Na V) and segmental sodium handling were investigated in conscious rats. Low-dose endothelin decreased renal plasma flow by 26% without affecting glomerular filtration rate and sodium excretion. High-dose endothelin reduced renal plasma flow, glomerular filtration rate, sodium excretion and lithium clearance by 57, 45, 38 and 52%, respectively. The fall in sodium excretion was not due to a direct effect of endothelin on tubular sodium transport since sodium excretion corrected by glomerular filtration rate and fractional proximal and distal sodium reabsorption did not change throughout the study. These results indicate that the impairment in renal perfusion is responsible for the antinatriuretic effect of endothelin in conscious rats.     

Coupling of NaHCO3 and NaCl reabsorption in dog kidneys during changes in plasma PCO2.

To study the relationship between proximal tubular reabsorption of bicarbonate, sodium, and chloride, the effects of changes in plasma PCO2 were examined in anesthetized dogs. Distal tubular reabsorption was inhibited by ethacrynic acid; plasma bicarbonate concentration was kept constant at 33.4 +/- 0.3 mM; glomerular filtration rate (GFR) was varied over a wide range to examine glomerulotubular balance (constant fractional reabsorption). Hypercapnia (PCO2, 112.0 +/- 2.5 mmHg) increased bicarbonate reabsorption by about 30%, and hypocapnia (PCO2, 19.8 +/- 0.6 mmHg) decreased reabsorption of bicarbonate by more than 50% and altered reabsorption of sodium, chloride, and bicarbonate in the molar ratios 2.7:1.6:1, respectively. During hypercapnia the range of glomerulotubular balance was extended to a GFR 125% of control. During hypocapnia glomerulotubular balance was present only at GFR below 50% of control; reabsorption of bicarbonate sodium, and chloride was constant at GFR exceeding 50% of control. During metabolic acidosis hypercapnia had no significant effect on reabsorption of bicarbonate, sodium, and chloride. These observations support the hypothesis that bicarbonate reabsorption is the main driving force for osmotic reabsorption of water and NaCl in the proximal tubules.     

Renal Na+-K+-ATPase in renin release

The effects of ouabain and furosemide on renin secretion, renal function, and renal Na+-K+-ATPase were investigated in anesthetized dogs. Furosemide (2 mg/kg) induced significant diuresis, natriuresis, an increase in renal blood flow (RBF), and a fivefold increase in renin secretory rate (RSR), but no changes in glomerular filtration rate (GFR). Infusion of ouabain (1 microgram . kg-1 . min-1) into one renal artery during furosemide diuresis increased fractional sodium excretion from 22 +/- 2 to 30 +/- 3% from the ipsilateral kidney but did not change urine flow, RBF, or GFR, whereas RSR fell to control values (698 +/- 203 to 137 +/- 43). When ouabain preceded furosemide, the rise in RBF and RSR induced by furosemide was abolished but sodium excretion increased. Ouabain infused in vivo inhibited Na+-K+-ATPase in microsomal fractions from cortex (34%) and medulla (27%) as compared with control. Neither saline nor furosemide exerted any effect on Na+-K+-ATPase. Moreover, the effect of ouabain alone on Na+-K+-ATPase was not different from that of ouabain plus furosemide. No changes in Mg2+-ATPase were detected in any of the experiments. These results indicate that inhibition of renal Na+-K+-ATPase abolishes furosemide-induced renin secretion despite potentiation of the natriuretic effect of the diuretic. It is apparent that the level of activity of Na+-K+-ATPase is of prime importance for renin secretion. In addition, ouabain may act directly on the juxtaglomerular cells to inhibit renin secretion.     

Renal Lithium Clearance during Dehydration and Rehydration with Water or 0.9% NaCl in the Rat

Male albino rats fed a diet containing lithium were dehydrated by 24 h of water deprivation and then rehydrated with demineralized water or 0.9 % NaCl. Renal lithium clearance decreased during rehydration with water. Rehydration with 0.9 % NaCl prevented the fall in the rate of urinary lithium elimination. The decrease in renal lithium clearance in the rats rehydrated with water was due to an increased fractional reabsorption of lithium in the renal tubules and was associated with a decrease in renal sodium clearance. The relationship between the renal elimination of sodium, potassium, and lithium during rehydration is discussed.     

Bicarbonate reabsorption in chronic renal failure studies in man and the rat

Bicarbonate reabsorption during bicarbonate loading was measured in rats and in patients with chronic renal failure (CRF) and in normal human subjects. Bicarbonate reabsorption expressed as Tm/GFR was not significantly different between normal and CRF rats despite the fact that fractional chloride excretion was significantly greater (an indication of volume expansion) in CRF rats than in normals. The ratio of absolute bicarbonate reabsorption/absolute sodium reabsorption, a parameter which corrects for the influence of volume on bicarbonate reabsorption, was significantly higher in CRF rats than in normals. In patients with CRF, bicarbonate reabsorption expressed either as Tm/GFR or as the ratio of absolute bicarbonate reabsorption/absolute sodium reabsorption was not different from that of the normal subjects. In patients with CRF, glomerular filtration rate (GFR) varied between 3 and 47 ml/min. The ratio of absolute bicarbonate reabsorption/absolute sodium reabsorption was inversely and significantly related to GFR, i.e. as nephron mass decreases sodium bicarbonate is preferentially reabsorbed over sodium chloride. These data demonstrate that in CRF bicarbonate reabsorption is enhanced relative to that of sodium and chloride in man.     

Independence of onset of compensatory kidney growth from changes in renal function.

Renal function was measure before and shortly after uninephrectomy in mice to evaluate if work expended in the reabsorption of glomerular filtrate plays a role in the initiation of compensatory growth. To exclude the possibility of small but undetectable increments in glomerular filtration rate and absolute sodium reabsorption these functions were experimentally reduced immediately after uninephrectomy and sham nephrectomy. The onset of growth was indicated by an increased rate of [14C]choline incorporation into phospholipid in renal cortical slices. [14C]choline incorporation increased significantly only after uninephrectomy and remained unchanged after sham operation regardless of the magnitude or direction of the concurrent change in sodium reabsorption. The rate of incorporation increased by 40 +/- 8% (P less than 0.005) in uninephrectomized animals whose sodium reabsorption was reduced by 34 +/- 6% (P less than 0.001) and rose 45 +/- 11% (P less than 0.005) when sodium reabsorption remained unchanged. These results indicate that compensatory kidney growth is not triggered by an increase in renal work expended in the reabsorption of glomerular filtrate; in fact, it can occur when reabsorptive work is substantially decreased.     

Nephrotoxicity of cyclosporine in humans: effect of cyclosporine on glomerular filtration and proximal tubular reabsorption

Summary The chronic nephrotoxic effects of cyclosporine (CsA) include proximal tubular atrophy and vacuolization. This study investigated the effect of CsA on renal hemodynamics and segmental electrolyte transport in CsA-treated patients. The clearance of inulin (C_In) and PAH para-amino-hippuric acid (C_PAH) was determined; proximal tubular function was studied using a lithium clearance method and calculating tubular phosphate reabsorption per milliliter of glomerular filtrate (TP/C_In). Twenty patients without renal disease were investigated: ten treated with CsA because of nonrenal grafting (group 1) and ten healthy volunteers (group 2). The results obtained were compared with those from 20 renal allograft recipients, of whom ten were treated with CsA and methylprednisolone (group 3) and ten with azathioprine and methylprednisolone (group 4). C_In and C_PAH were significantly impaired in patients treated with CsA. No significant impairment of lithium clearance as induced by CsA was observed. The fractional excretion of lithium was slightly increased in patients treated with CsA compared to their respective controls. TP/C_In was lower in graft recipients compared to controls; no impairment of phosphate reabsorption as induced by CsA was found. The fractional tubular excretion of lithium was slightly increased compared to controls, rising evidence that proximal tubular reabsorption of lithium was decreased. Tubular reabsorption of phosphate was not impaired. The decrease in glomerular filtration and renal perfusion during chronic treatment with CsA was accompanied by a reduced proximal reabsorptive capacity, as was shown by lithium clearance. Our data do not support the hypothesis that functional parameters of the proximal tubular system can be used as indicators of CsA-induced nephrotoxicity.Abbreviations C_In inulin clearance - C_Li lithium clearance - CPAH clearance of para-aminohippuric acid - C_PO4 phosphate clearance - Aza azathioprine - CsA cyclosporine A - GFR glomerular filtration rate - MP methylprednisolone - TmP threshold phosphate concentration - TP/C_In tubular phosphate reabsorption/ml inulin clearance - TP/GFR tubular phosphate reabsorption/ml glomerular filtration rate Supported by a grant from the A. Krupp von Bohlen und Halbach Foundation, D-45133 Essen, Germany     

Time course of the renal functional response to partial nephrectomy: measurements in conscious rats

Previous investigations into the functional responses of the surviving nephrons following reductions in renal mass have been performed largely in anaesthetized animals and have taken little account of how the compensatory changes develop with time. The present study has assessed a method for determining glomerular filtration rate (GFR) in unrestrained, uncatheterized, conscious rats (plasma disappearance of (99m)Tc-diethylenetriamene pentaacetic acid (DTPA)) and has used this method to document the time course of the changes in GFR over a 32 day period following uninephrectomy or 5/6 nephrectomy. Concurrent measurements of excretion rates and of the clearance of lithium (the latter being an index of end-proximal fluid delivery) provided information on changes in overall tubular function and segmental reabsorption. After uninephrectomy, the GFR of the remaining kidney (compared with that of a single kidney of sham-operated animals) increased maximally (by approximately 50%) within 8 days; after 5/6 nephrectomy, the increase in the GFR of the remnant kidney was maximal (at approximately 300%) within 16 days. Overall excretion rates of sodium and potassium were well maintained in partially nephrectomized animals throughout the period of study, while the excretion of water increased (by approximately 30% after uninephrectomy and by approximately 120% after 5/6 nephrectomy), partly as a result of the compensatory increases in GFR but mainly as a consequence of moderate (after uninephrectomy) or marked (after 5/6 nephrectomy) reductions in fractional reabsorption. During the early period after 5/6 nephrectomy, potassium excretion sometimes exceeded the filtered load, indicating net secretion. Lithium clearance data indicated that the changes in tubular function after 5/6 nephrectomy include a reduction in fractional reabsorption in the proximal tubule, whereas after uninephrectomy any such effect on the proximal tubule is minor and transient.     

Autoregulation of nephron filtration rate in the dog assessed by indicator-dilution technique.

Micropuncture studies were conducted in anesthetized dogs to evaluate single nephron glomerular filtrate rate (SNGFR) and SNGFR autoregulation when assessed by means of an indicator-dilution technique (SNGFRID), which does not require interruption of distal volume delivery. In 18 dogs, control renal arterial pressure was 124 +/- 11 mmHg (SD), renal blood flow (RBF) was 185 +/- 58 ml/min, and whole kidney GRF was 37 +/- 7 ml/min. SNGFRID averaged 57 +/- 15 nl/min and was significantly lower than SNGFR determined on the basis of total collections (SNGFRTC) from proximal tubules (75 +/- 17 nl/min). However, SNGFRID was not significantly different from the overall average SNGFR of 62 +/- 12 nl/min estimated from whole kidney GFR and the total number of glomeruli (613,000 +/- 74,000). In 10 animals, renal arterial pressure was reduced to an average of 94 +/- 8 mmHg; whole kidney autoregulation was highly efficient and average RBF and GRF remained within 1 and 3% of their control values. Likewise, SNGFRID was not significantly altered at 52 +/- 17 and 52 +/- 16 nl/min. In contrast, SNGFRTC decreased significantly from 72 +/- 17 to 51 +/- 13 nl/min. These results indicate that the indicator-dilution technique provides a reliable assessment of SNGFR and allows the manifestation of single nephron autoregulatory behavior. They provide further support for the hypothesis that maintenance of distal volume delivery may be a necessary aspect of the autoregulation phenomenon.     

Role of Endothelin ETA Receptor Antagonism in the Post-Transplant Renal Response to Angiotensin II in the Rat

The role of endothelins in the renal damage associated with ischaemic-reperfusion (I-R) injury during organ transplantation was determined by selective blockade of the ET(A) receptors with the receptor antagonist ABT-627. The integrity of kidney function was determined 2 and 8 weeks after transplantation by investigation of the renal response to angiotensin II. Under pentobarbitone anaesthesia (70 mg x kg(-1), I.P.), rats underwent a right nephrectomy. Transplantation of the left kidney was performed after 2 h cold ischaemia without or with ABT-627 treatment. Control animals underwent left renal denervation. The renal response to angiotensin II was measured 2 weeks later following blockade of endogenous production of angiotensin II with captopril. A further transplant group was allowed to recover for 8 weeks before the terminal study. In the control group, angiotensin II reduced renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (UV), and fractional sodium excretion (FE(Na)) by 29 +/- 5 %, 19 +/- 4 %, 25 +/- 4 % and 32 +/- 7 %, respectively. Conversely, in the transplant group, angiotensin II left RBF unchanged and increased GFR (59 +/- 12 %) and UV (93 +/- 8 %). FE(Na) decreased by 24 +/- 9 %. In both the transplant group treated with ABT-627 and the long-term recovery group, the renal response to angiotensin II was normalised. In conclusion, renal transplantation following 2 h cold I-R injury resulted in a temporary abnormal renal response to angiotensin II, which was reversed by ET(A) receptor antagonism at the time of transplantation.     

Renal, cardiovascular and endocrine responses of fetal sheep at 0.8 of gestation to an infusion of amino acids

Amino acid infusions increase renal blood flow (RBF) and glomerular filtration rate (GFR) and stimulate tubular reabsorption in adults. To characterize the effects of amino acids on fetal renal haemodynamics, tubular sodium reabsorption, acid-base homeostasis and plasma renin levels, 11 chronically catheterized fetal sheep aged 121 ± 1 days (term ∼150 days) were infused i.v for 4 h with alanine, glycine, proline and serine (0.1, 0.1, 0.06 and 0.06 mmol min⁻¹, respectively) in 0.15 m saline at 0.165 ml min⁻¹. Eight control fetuses were given saline. During amino acid infusion, plasma amino acid levels increased up to 20-fold (   P < 0.005  ). GFR increased by 50 ± 8 % (   P < 0.001  ); there was only a small transient increase in RBF. Proximal fractional sodium reabsorption fell from 74.6 ± 2.9 to 55.5 ± 5.4 % (   P < 0.005  ). Distal sodium delivery increased, but a smaller percentage of this distal sodium load was reabsorbed (   P < 0.005  ). Thus fractional sodium reabsorption fell from 95.5 ± 0.9 to 81.4 ± 2.0 % (   P < 0.005  ). There was a large diuresis, natriuresis, kaliuresis and increase in osmolar excretion (   P < 0.005  ). Plasma sodium and chloride concentrations fell (   P < 0.005  ). Plasma osmolality did not change. Plasma renin levels fell (   P < 0.05  ), cortisol levels increased (   P < 0.05  ), and there was a compensated metabolic acidosis. Thus the fetal sheep kidney demonstrated a remarkable functional capacity to respond to amino acid infusion. The increase in filtration fraction and the lack of an increase in RBF suggest that efferent arteriolar vasoconstriction occurred, a very different response from the renal vasodilatation seen in adult animals.