Effect of glutathione depletion on urinary acidification in the rat

Glutathione (GSH) depletion by diethyl maleate (DEM) administration and its rapid repletion were associated with the development of a moderate acidosis in the rat. The acidosis observed after DEM treatment could be a consequence of an impairment of lactate metabolism. GSH-depleted rats also showed an increased urine pH and a higher bicarbonate fractional excretion compared with control rats. Renal bicarbonate excretion was magnified when blood bicarbonate levels were normalized by means of a bicarbonate infusion in GSH-depleted rats; however, the amount of bicarbonate excreted in the urine was a very small fraction (less than 5%) of the calculated filtered load. GSH-depleted rats failed to elevate the relation urine minus blood (U-B) pCO2 as compared with control rats when they were subjected to a high bicarbonate load to the distal portions of the nephron. All these data were consistent with a distal renal tubular acidosis due to GSH depletion which could participate in the maintenance of the systemic acidosis, although it is unlikely that it is the primary cause of the acidosis.     

The effect of Ringer solution induced extracellular volume expansion on kidney function

The present study quantitated the effects of extracellular volume expansion on sodium and water excretion in 118 anesthetized dogs. The animals received a priming injection of 10 ml kg-1 Ringer solution i.v. which was followed by a constant Ringer solution infusion at a rate of 0.25 ml.min-1.kg-1 until the end of the experiment. Fifteen minutes after the start of the constant infusion the renal parameters were examined in 11 subsequent 15 min periods (the total time was 3 hours). Volume expansion produced no significant change in arterial blood pressure, glomerular filtration rate (GFR), plasma sodium and potassium concentration or, haematocrit, but did reduce the CPAH from 284 ml.min-1 to 218 ml.min-1 (the data were calculated for 100 gram wet kidney weight). There were constant significant increases in the urinary excretion rate from 0.84 ml.min-1 to 4.06 ml.min-1 and the 39% of the infused water was excreted during the experiment. Volume expansion also caused a significant increase in sodium excretion during the three first periods from 120 mumol.min-1 to 329 mumol.min-1 followed by a small but significant decrease. The sodium excretion at the end of the experiment was 221 mumol.min-1 and the 23% of the infused sodium was excreted in the course of the experiment. The increase of the water excretion during the volume expansion was associated with fall of the urine osmolality and the urine because hypoosmotic as compared to the plasma. We have provided evidence that vasopressin was not involved in the control of water excretion in our experiments. It is concluded that neither filtered sodium nor decreased aldosterone secretion can account for the increase in sodium excretion that occurs after Ringer solution loading in the dog. It has been proposed that a decrease in plasma protein concentration may decrease passive sodium reabsorption due to oncotic forces in the proximal tubule. The Ringer solution diuresis elicits a rise in medullary blood flow, thereby causing a washout of medullary sodium. This might dissipate the osmotic force for the back-diffusion of water from the collecting duct. Our studies indicate that the response of the diluting segments of the distal nephron to increased delivery of sodium depends upon the presence or absence of volume expansion. However the increase of the distal tubular loading activates the tubuloglomerular feedback which increases the proximal tubular reabsorption. Based on these assumptions our studies provide further evidence that the tubuloglomerular feedback regulates the blood pressure in the peritubular capillaries in the cortex around the proximal tubules.     

Evidence against bicarbonate reabsorption in the ascending limb, particularly as disclosed by free-water clearance studies.

Bicarbonate reabsorption in the thick ascending limb of Henle's loop was examined by studies of free-water clearance (CH2O) and free-water reabsorption (TcH2O). During maximal water diuresis in the dog, CH2O/GFR was taken as an indes of sodium reabsorption in, and urine flow (V/GFR) as an index of delivery of filtrate to, this scarbonate, infusion of a nonreabsorbable solute (hypotonic mannitol) and administration of an inhibitor of bicarbonate reabsorption (acetaent, but less than that achieved with hypotonic saline infusion. This suggests that sodium that sodium bicarbonate is not reabsorbed in the ascending limb. Rather, it is the sodium chloride, swept out of the proximal tubule by osmotic diuresis due to nonreabsorbed mannitol or sodium bicarbonate, that is reabsorbed in the ascending limb thereby increasing CH2O, whereas the nonreabsorption of mannitol and sodium bicarbonate results in a depressed CH20 per unit V when compared with hypotonic saline. V/GFR is not a satisfactory index of delivery to the ascending limb during osmotic diuresis, since it includes water obligated by nonreabsorbable solutes. When a better index of delivery, the sum of the clearances of chloride (CC1) and free-water (CH2O) is used, hypotonic bicarbonate infusion, hypotonic mannitol infusion and acetazolamide administration increase CH2O/GFR per unit delivery to the same extent as odes hypotonic saline infusion. Studies in dogs and rats on TcH2O also indicate that sodium bicarbonate is an impermeant solute in the ascending limb. Osmotic diuresis due to sodium bicarbonate diuresis, produced either by inhibition of sodium bicarbonate reabsorption (acetazolamide, L-lysine mono-hydrochloride) or infusion of sodium bicarbonate, or mannitol diuresis both produced marked chloruresis and increased TcH2O to the same extent as did hypertonic saline infusion. If chloride excretion was almost eliminated by hemodialysis against a chloride-free dialysate (dogs) or prolonged feeding of a salt-free diet (rats), TcH2O formation was unimpaired if hypertonic saline was infused but virtually obliterated during mannitol or sodium bicarbonate diuresis. Sodium reabsorption in the ascending limb, therefore, appears to be dependent upon chloride as the accompanying anion. At any given rate of bicarbonate excretion, more cloride is delivered out of the proximal tubule (as estimated from CC1 + CH2O) with hypotonic sodium bicarbonate infusion than with acetazolamide administration. This suggests that magnitude of the chlorutesis accompanying bicarbonate diuresis depends, not only on osmotic diuresis due to nonreabsorbed sodium bicarbonate, but also on the extent to which concomitant changes in effective extracellular volume influence overall sodium chloride reabsorption.     

Extracorporeal bicarbonate space after bicarbonate or a bicarbonate-carbonate mixture in acidotic dogs

The effects of sodium bicarbonate and a bicarbonate-carbonate mixture on expired CO2 and the volume of distribution of bicarbonate were studied in eight anesthetized, paralyzed, and ventilated dogs made acidotic with HCl (5 mmol/kg) infused over 90 min. Both sodium bicarbonate and Carbicarb resulted in systemic alkalinization and comparable increases in the serum bicarbonate at 50 min (7.07 +/- 0.91 vs. 7.99 +/- 0.77, respectively; P = NS). Sodium bicarbonate infusion resulted in an increase in CO2 excretion that accounted for a fractional CO2 excretion of 0.20 +/- 0.09, whereas infusion of a bicarbonate-carbonate mixture resulted in a fractional CO2 excretion of -0.06 +/- 0.09 (P less than 0.01). The uncorrected volume of distribution of bicarbonate after sodium bicarbonate infusion was higher than that seen with the bicarbonate-carbonate mixture (0.60 +/- 0.07 vs. 0.34 +/- 0.03 l/kg; P less than 0.01). However, when the volume of bicarbonate distribution was corrected for expired CO2, there was no difference between treatment with sodium bicarbonate and the bicarbonate-carbonate mixture (0.44 +/- 0.07 vs. 0.38 +/- 0.04 l/kg; P = NS). These data demonstrate that, in this animal model of acidosis, sodium bicarbonate treatment of systemic acidosis is accompanied by a generation of a considerable amount of CO2, whereas treatment with a bicarbonate-carbonate mixture is not. This suggests that in states of impaired ventilation, a bicarbonate-carbonate mixture may offer more efficient systemic alkalinization and may be associated with less CO2 generation than sodium bicarbonate.     

A stop-flow study of intrarenal effects of atrial natriuretic factor

We performed paired series of stop-flow studies on six mongrel dogs to determine a possible nephron site of action of synthetic atrial natriuretic factor (ANF). The initial free-flow response to intrarenal infusion of 5 micrograms/min of synthetic ANF into mannitol-expanded dogs resulted in an increased urine flow rate (6.81 +/- 0.88 to 9.00 +/- 1.17 ml/min, P less than 0.05) and a 40% increase in sodium excretion (496 +/- 110 to 694 +/- 166 meq/min, P less than 0.025) when compared to paired control periods. Renal blood flow did not change, but the glomerular filtration rate increased 4% (47 +/- 5 to 49 +/- 6 ml/min, P less than 0.05). The filtered load of sodium increased 4% (P less than 0.05), and the fractional sodium excretion increased by 35% (P less than 0.01). Stop-flow experiments showed no difference in tubular sodium concentration or in the fractional sodium-to-inulin ratio at the nadir of sodium concentration, suggesting that no differences existed in distal tubular sodium handling. Further, no apparent differences were detected in collections representing the more proximal portions of the nephron. While we were able to demonstrate marked natriuresis in response to synthetic ANF, no tubular effect was discernible, and the natriuresis obtained appears to be predominantly a function of hemodynamic effects.     

Effect of somatostatin on renal water handling in the dog

When somatostatin was infused into the left renal artery of anaesthetized, hydropenic dogs in doses ranging from 1 to 10 micrograms/min, it produced an increased flow of a more dilute urine from the ipsilateral kidney. Similar infusions in dogs undergoing a maximal water diuresis had no effect. If aqueous antidiuretic hormone (ADH) was administered intravenously into water-loaded dogs prior to the intraarterial infusion of somatostatin, this latter peptide was able to produce an augmented flow of a more dilute urine from the ipsilateral kidney. If the left kidney was made to excrete a concentrated urine in the face of maximal water loading by restricting arterial perfusion, then the infusion of somatostatin had no effect on urinary dilution, though this peptide could increase water excretion in hydropenic dogs when the left kidney was similarly restricted as to arterial inflow. In dogs undergoing a water diuresis that were given cyclic AMP (4 mg/min) into the left renal artery, a decrease in ipsilateral water excretion was observed. The subsequent infusion of somatostatin produced no urinary dilution. We conclude that somatostatin increases renal water excretion by antagonizing the ADH effect on the renal tubule, and that this event probably occurs at a pre-cAMP site within the cell.     

Studies on renal excretion of potassium in the dik-dik antelope

1. In a study on the renal handling of potassium by the dik-dik antelope, plasma and urine samples were analysed for potassium, sodium and creatinine concentrations and osmolality during dehydration and intra-ruminal loading of potassium solutions. 2. The fractional excretion of potassium was 0.64 during the control period and rose up to as high as 2.3 during potassium loading. Urinary osmolality and potassium concentration decreased as the urine volume increased but the total amounts of potassium excreted were independent of urine volume. 3. Potassium loading led to a steady increase in its urinary excretion but a decrease in plasma potassium concentration was observed. This observation casts doubt on the hypothesis that alterations in potassium intake produce parallel alterations in plasma potassium concentration (which supposedly stimulates or depresses potassium excretion) and thereby maintain potassium homeostasis. 4. A possible alternative signal for increased potassium excretion following increased intake is discussed.     

Effects of alpha-adrenergic blockade on sodium excretion in normal and chronic salt retaining dogs.

The alpha-adrenergic blocking agent phenoxybenzamine (PBA) was administered intravenously (10 mug kg-1 min-1) during a steady state water diuresis under pentothal anesthesia to six normal dogs, six dogs with chronic throacic inferior vena cava constriction and ascites (caval dogs) and seven dogs chronically salt depleted by sodium restriction and furosemide administration. In normal dogs urinary sodium excretion increased significantly from 265+/56 (SEM) to 370+/65 muequiv./min, whereas no increase in sodium excretion was noted in either caval dogs or salt depleted animals after PBA. In all three groups urine volume, fractional free water clearance and distalsodium load did not change significantly. In normal dogs, tubular sodium reabsorption decreased significantly from 73.4+/2.8% to 63.1+/4.0%, whereas no change was noted in caval or salt depleted dogs. Blood pressure and renal hemodynamics were not significantly altered by PBA administration in any group. These data demonstrate a natriuretic effect of alpha-adrenergic blockade in normal dogs with the major effect in the water clearing segment of the nephron. The absence of any effect in chronic caval or salt depleted dogs suggests that increased alpha-adrenergic activity does not play a significant role in the sodium retention of these animals.     

Evidence supporting a physiological role for proANP-(1-30) in the regulation of renal excretion

The experiments, performed in pentobarbital sodium-anesthetized rats, consisted of a 1-h equilibration period followed by two 30-min control periods. Subsequently, synthetic rat pro atrial natriuretic peptide (ANP) [proANP-(1-30)] (n = 8) was given as a bolus of 10 microg in 1 ml of 0.9% saline followed by an infusion at 30 ng/min (20 microl/min) for six additional periods. Control rats (n = 6) received only 0.45% saline in the appropriate volumes. Mean arterial pressure, renal blood flow, and glomerular filtration rate did not change significantly in either group during the proANP-(1-30) infusion. Urine flow and potassium excretion increased approximately 50% in the proANP-(1-30)-infused group only (P < 0.05). Sodium excretion and fractional excretion of sodium, expressed as the change from their own baselines, were significantly increased by the proANP-(1-30) infusion (P < 0.05), whereas cGMP excretion was similar in both groups. These results suggest that the rat sequence of proANP-(1-30) produces a natriuresis in the rat independent of changes in hemodynamics and renal cGMP production. In a second study, rats (n = 8) were prepared as above and pretreated with 0.4 ml iv of rabbit serum containing an antibody directed against proANP-(1-30) (anti-proANP group). The rats were volume expanded with 3 ml of 6% albumin in Krebs and observed for 3 h to determine if the anti-proANP would attenuate the responses to volume expansion. Control rats (n = 7) received 0.4 ml of normal rabbit serum. The elevation in potassium excretion in response to volume expansion was significantly attenuated in the anti-proANP group (P < 0.05). Sodium excretion and urine flow responses also tended to be reduced but not significantly. These results suggest that in the rat, proANP-(1-30) plays a physiological role in regulating renal excretion.     

Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 micrograms/min, i.v.), an alpha 1-adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (-67 +/- 9 vs. -33 +/- 8%), glomerular filtration rate (-60 +/- 9 vs. -7 +/- 20%), urine flow (-61 +/- 7 vs. -24 +/- 11%), sodium excretion (-51 +/- 15 vs. -32 +/- 21%), and fractional excretion of sodium (-50 +/- 9 vs. -25 +/- 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (-54 +/- 10 vs. -30 +/- 14%), glomerular filtration rate (-51 +/- 11 vs. -19 +/- 17%), urine flow (-55 +/- 10 vs. -39 +/- 10%), sodium excretion (-70 +/- 9 vs. -59 +/- 11%), and fractional excretion of sodium (-53 +/- 10 vs. -41 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal function of rats in response to 37 days of head-down tilt

Spaceflight induces changes in human renal function, suggesting similar changes may occur in rats. Since rats continue to be the prime mammalian model for study in space, the effects of chronic microgravity on rat renal function should be clarified. Acute studies in rats using the ground-based microgravity simulation model, head-down tilt (HDT), have shown increases in glomerular filtration rate (GFR), electrolyte excretion, and a diuresis. However, long term effects of HDT have not been studied extensively. This study was performed to elucidate rat renal function following long-term simulated microgravity. Chronic exposure to HDT will cause an increase in GFR and electrolyte excretion in rats, similar to acute exposures, and lead to a decrease in the fractional excretion of filtered electrolytes. Experimental animals (HDT, n=10) were tail-suspended for 37 days and renal function compared to ambulatory controls (AMB, n=10). On day 37 of HDT, GFR, osmolal clearance, and electrolyte excretion were decreased, while plasma osmolality and free water clearance were increased. Urine output remained similar between groups. The fractional excretion of the filtered electrolytes was unchanged except for a decrease in the percentage of filtered calcium excreted. Chronic exposure to HDT results in decreased GFR and electrolyte excretion, but the fractional excretion of filtered electrolytes remained primarily unaffected.     

Volume expansion during NOS substrate donation with L-arginine: regulatory offsetting of renal response?

The responses to infusion of nitric oxide synthase substrate (L-arginine 3 mg.kg(-1).min(-1)) and to slow volume expansion (saline 35 ml/kg for 90 min) alone and in combination were investigated in separate experiments. L-Arginine left blood pressure and plasma ANG II unaffected but decreased heart rate (6 +/- 2 beats/min) and urine osmolality, increased glomerular filtration rate (GFR) transiently, and caused sustained increases in sodium excretion (fourfold) and urine flow (0.2 +/- 0.0 to 0.7 +/- 0.1 ml/min). Volume expansion increased arterial blood pressure (102 +/- 3 to 114 +/- 3 mmHg), elevated GFR persistently by 24%, and enhanced sodium excretion to a peak of 251 +/- 31 micromol/min, together with marked increases in urine flow, osmolar and free water clearances, whereas plasma ANG II decreased (8.1 +/- 1.7 to 1.6 +/- 0.3 pg/ml). Combined volume expansion and L-arginine infusion tended to increase arterial blood pressure and increased GFR by 31%, whereas peak sodium excretion was enhanced to 335 +/- 23 micromol/min at plasma ANG II levels of 3.0 +/- 1.1 pg/ml; urine flow and osmolar clearance were increased at constant free water clearance. In conclusion, L-arginine 1) increases sodium excretion, 2) decreases basal urine osmolality, 3) exaggerates the natriuretic response to volume expansion by an average of 50% without persistent changes in GFR, and 4) abolishes the increase in free water clearance normally occurring during volume expansion. Thus L-arginine is a natriuretic substance compatible with a role of nitric oxide in sodium homeostasis, possibly by offsetting/shifting the renal response to sodium excess.     

The effect of infusion of hypertonic saline on glomerular filtration rate and arginine vasotocin, prolactin and aldosterone in the domestic chicken

Domestic fowl were infused for 60 min with isotonic saline followed by 90 min with hypertonic saline. Plasma electrolyte concentrations, osmolality and haematocrit were measured. Urine electrolyte excretion rates, osmolar output and urine flow rates were also monitored. From these results fractional excretions of electrolytes were calculated. The renal function markers inulin and ρ-amino hippuric acid were infused to enable the measurement of glomerular filtration rate and plasma clearance of ρ-amino hippuric acid, respectively. Plasma samples were also taken to assay for the hormones prolactin, aldosterone and arginine vasotocin. Plasma electrolytes and osmolality, fractional excretion of electrolytes and osmolar output all increased, while haematocrit decreased, throughout the experiment. However, no significant change was found in urine flow rate and little change was seen in glomerular filtration rate. The clearance of ρ-amino hippuric acid, which provides an indication of renal plasma flow, increased during hypertonic saline infusion. Plasma concentrations of aldosterone and prolactin decreased during the experiment and plasma concentrations of arginine vasotocin increased. Infusion of hypertonic saline had no consistent effect on glomerular filtration rate, which may be due to conflicting influences of expansion of the extracellular fluid volume and increased plasma osmolality. Accepted: 19 January 1998     

Effect of acetazolamide on salivary excretion of inorganic ions in sheep

The salivary excretion of inorganic ions in sheep was studied parallel with infusion of salt solutions of different composition through the temporary isolated rumen cavityin vivo. The amount of Na⁺ excreted with saliva decreases by 15–55% after an intravenous loading with acetazolamide (50 mg/kg of animal weight) and by 25–55%, of K⁺, which represents a part of the ion excretion with participation of H⁺ exchanges. The Na⁺ excretion that is not inhibited by acetazolamide in sheep is about 40 mmol/10 kg of exchange mass per 1 h in all experiments with loading.     

Absorption of cadmium after a long-term oral administration of cadmium to dogs

A long-term experiment using beagle dogs to investigate the absorption of cadmium was conducted. The dogs in the experimental groups were given a commercial diet and pelleted food containing 1, 3, 10, 50, and 100 mg of cadmium per day. The cadmium concentration in the blood increased continuously, gradually reaching a steady state following the administration of cadmium. The cadmium excreted daily in urine increased continuously. The cumulative excreted amount of cadmium in urine was calculated by using the trapezoidal rule based on the data of excretion of cadmium in urine. Then the absorbed fraction of administered cadmium was estimated on the basis of the relationship between the cumulative excreted amount of cadmium in urine and the cumulative administered dose of cadmium after the cadmium concentration in blood reached a steady state. The absorbed fraction of cadmium decreased with an increase in the administered dose of cadmium. A dose-dependent increase between the absorbed amount and the administered dose was observed.     

Influence of augmentation of excretory renal mass on renal function after alpha-receptor blockade

The effect of renal function of an augmentation of the excretory renal mass was investigated in 10 dogs without drug treatment and in 10 animals with alpha-receptor blockade. In the untreated group, augmentation of excretory renal mass by transplantation into the neck of one pair of kidneys isolated from another animal caused the following changes in the kidneys in situ: marked elevation in CPAH, slight decrease in Cinulin, slight diminution of urine excretion and a pronounced fall in sodium excretion. The amount of urine and sodium excreted by the four kidneys was identical with that previously excreted by the two kidneys in situ. In animals with alpha-receptor blockade, augmentation of the excretory renal mass had the following consequences in the in situ kidneys, CPAH, and Cinulin remained unchanged while urine and sodium excretion decreased to the same extent as in the untreated control group. The amount of urine and of sodium excreted by the four kidneys was the same as that excreted by the kidneys in situ, prior to transplantation of isolated kidneys, i.e. before the augmentation of excretory renal mass. It seems that the decrease in sodium excretion of the kidneys in situ was not due to the haemodynamic changes evoked by the load on the circulation; it was rather consequence of some quick, presumably humoral, regulation. The diminution of sodium excretion in the kidneys in situ after augmentation of the excretory renal mass has been ascribed to an increased utilization by the four kidneys of the natriuretic factor(s), i.e. to a diminution in the plasma level of the natriuretic hormone.     

Renal effects of dopamine and ANP in high volume expanded rats

Both dopamine (DA) and atrial natriuretic peptide (ANP) have been postulated to exert similar effects on the kidney, participating in the regulation of body fluid and sodium homeostasis. In the present study, experiments were performed in anesthetized and isotonic sodium chloride volume expanded rats. After acute volume expansion at 15 % of body weight during 30 min, glomerular filtration rate, urine output, sodium excretion, fractional sodium excretion, proximal and distal sodium excretion and blood pressure were measured. In additional groups we administered ANP or haloperidol or the combination of both to volume expanded animals. Blockade of DA receptors with haloperidol, attenuated diuretic and natriuretic responses to volume load. Proximal sodium excretion was not modified by haloperidol in all experimental groups of rats. Reduction in distal tubular excretion was induced by haloperidol in saline infusion expanded rat but not in ANP treated expanded animals. In conclusion, when exaggerated volume expansion is provoked, both DA and ANP exert renal tubular events, but ANP have a major central role in the regulation of renal sodium handling.     

Altered renal response to acute volume expansion in transgenic rats harboring the human tissue kallikrein gene

The renal response to acute volume expansion was investigated in transgenic (TGR) rats harboring the human tissue kallikrein gene. After a primer injection of 0.9% NaCl (3 ml/100 g, i.v), Sprague-Dawley (SD) or TGR rats received a continuous infusion of 0.9% NaCl (15 microl/100 g/min, i.a.) through a catheter placed into the carotid artery. Acute volume expansion was produced by a second injection of 0.9% NaCl (2 ml/100 g, i.v.) 65 min after the first injection. Plasma vasopressin (AVP) and atrial natriuretic peptide (ANP) concentration was measured before and within 10 min of volume expansion. TGR animals presented a blunted response to acute volume expansion evidenced by an attenuated increase in total and fractional water and sodium excretion. Before or after volume expansion, plasma AVP and ANP did not differ between SD and TGR. Pre-treatment with the BK-B2 antagonist HOE-140 (7.5 microg/100 g. i.a) partially improved the renal response of TGRs and severely blunted the response in SD rats. These data show that TGR (hKLK1) rats have an impaired renal response to acute volume expansion that can not be accounted for by changes in the release of AVP or ANP.     

The actions of cortisol on fetal renal function

Renal function was studied in 6 fetal sheep, aged 126-135 days, before and after 3 injection of 15 mg of cortisol given at intervals of 12 h. Cortisol caused a significant rise in both renal blood flow (P less than 0.05) and glomerular filtration rate (P less than 0.005), and in urine flow rate (P less than 0.02) but it did not consistently cause a natriuresis. The urinary pH was unchanged following cortisol treatment, but bicarbonate excretion increased. Urinary phosphate excretion was increased (P less than 0.005) because of a rise in filtered phosphate and a fall in phosphate reabsorption. The titratable acid excretion increased (P less than 0.005) but urinary ammonium excretion did not. The total amount of sodium reabsorbed increased after cortisol but the amount of sodium reabsorbed in the proximal tubule did not increase, so fractional reabsorption in the proximal tubule decreased from 61.7 +/- 4.1% to 47.3 +/- 4.2% (P = 0.01). The total amount of sodium reabsorbed in the distal tubule increased and distal fractional reabsorption increased from 33.3 +/- 2.4% to 47.3 +/- 4.2% (P less than 0.01). Cortisol may increase the capacity of the immature kidney to play a role in fluid and electrolyte homeostasis by increasing glomerular filtration rate and delivering more sodium and water to the distal nephron where the reabsorption of sodium and water can be modified independently and in accordance with need.     

Renal and systemic effects of synthetic atrial natriuretic factor

A synthetic peptide corresponding to a sequence of 26 amino acids contained in endogenous rat atrial natriuretic factor (ANF), was infused into one renal artery of anesthetized dogs for a comprehensive in vivo evaluation of the renal and systemic effects of pure ANF. The results proved conclusively that ANF acted directly on the kidney since urine volume and fractional excretion of sodium, potassium, chloride and calcium were elevated in a dose-related manner in the ANF-treated kidney, but were not significantly affected in the contralateral saline-infused organ. The maximum effects achieved with the synthetic ANF were higher than any reported following intravenous administration of crude extracts of rat atria and were similar to those produced by thiazide diuretics. In four of the five dogs studied, renal vascular resistance fell progressively as doses of ANF were increased. Glomerular filtration rate was not significantly elevated during ANF infusion, but was correlated with sodium excretion rates. Even though mean arterial pressure was progressively reduced, there was no significant change in heart rate and no stimulation of renin secretion. Arterial cyclic GMP concentration was higher in the basal state and rose more rapidly than did renal venous levels, indicating that increases in circulating concentrations of arterial cyclic GMP originated from an extrarenal source. Dose-related elevations in urinary cyclic GMP excretion could be explained by increased cyclic GMP filtration, by enhanced production in tubular cells, or by renal tubular secretion. Especially in the saline-infused kidney, there was a clear dissociation between excretion of cyclic GMP and fractional sodium excretion. We conclude that the synthetic ANF increased electrolyte excretion via a direct renal action which was not solely dependent upon changes in renal vasculature, renin secretion or cyclic GMP levels.