Extracellular Fluid Volume Expansion Research Articles

Effects of Kallikrein Inhibition with Aprotinin on Intrarenal Hemodynamics and Urinary Prostaglandin Excretion in Control and Saline-Loaded Conscious Rats

In conscious rats inhibition of kallikrein formation with aprotinin suppressed urinary prostaglandin (PG) E<sub>2</sub> excretion. This was associated with a decrease in inner cortical perfusion in the absence of changes in GFR or hippuran clearance. During acute expansion of the extracellular fluid volume (ECFV) with isotonic saline PGE<sub>2</sub> excretion significantly increased but was suppressed during stable ECFV expansion. With ECFV expansion GFR increased, while total and regional cortical perfusion remained unchanged. Aprotinin suppressed the early rise in PGE<sub>2</sub> excretion and reduced GFR and hippuran clearance as a result of decreased outer cortical perfusion. It is suggested that integrity of the kinin-prostaglandin system represents an important prerequisite for the functional adaptation of the kidney to acute expansion of the ECFV with isotonic saline.

Correction of metabolic acidosis by the kidney during isometric expansion of extracellular fluid volume.

In dogs with chronic hypochloremic metabolic alkalosis associated with ECFV contraction, plasma [HCO-3] ([HCO-3]p) normalizes during expansion of ECFV with a solution containing Cl- and HCO-3 in concentrations duplicating those in the plasma before expansion (isometric expansion). The kidney selectively rejects administered HCO-3 and retains Cl-. If this preferential Cl- less than HCO-3 reabsorptive selectivity were a characteristic renal response to ECFV expansion, isometric expansion during hyperchloremic acidosis would exacerbate the acid-base disturbance rather than correct it as it does in alkalosis. We examined the effect of isometric expansion in dogs with chronic hyperchloremic metabolic acidosis induced by HCl feeding or mineralocorticoid hormone deficiency. During expansion, as the expected decrease occurred in the fractional reabsorption of Na+, a lesser decrease occurred in fractional reabsorption of HCO-3, whereas a greater decrease occurred in fractional reabsorption of Cl-. The kidney selectively retained administered HCO3 and rejected Cl-. [HCO-3]p normalized. The shift to bicarbonate-selective from chloride-selective anion reabsorption during ECFV expansion in metabolic acidosis vs. metabolic alkalosis indicates that in response to ECFV expansion- the kidney selectively alters the ratio of bicarbonate to chloride concentration in the tubular reabsorbate in the direction that tends to normalize plasma acid-base composition, irrespective of the direction of deviation of the initial plasma bicarbonate concentration. The signal that initiates the shift in anion reabsorptive selectivity remains to be identified.

Effect of Cholera Toxin on Renal Tubular Reabsorption of Glucose and Bicarbonate

SummaryCholera toxin (CT) reduces tubular reabsorption of Na, Cl, Ca, Mg and P most probably through stimulation of a renal adenylate cyclase-cyclic AMP system, and it is possible that an increased production of nephrogenous cyclic AMP during extracellular fluid volume expansion may be partly responsible for the observed natriuresis. In order to further evaluate the role of renal cyclic AMP in renal tubular transport, we studied the effect of CT on glucose (TRG) and bicarbonate reabsorption (TRHCO3).During the period of maximal effect of CT on tubular transport (100-140 min of CT infusion into one renal artery) both the TRG and TRHCO3 were lower in the infused kidney than in the contralateral noninfused kidney; TRG as mg per 100 ml GFR was 254 ± 32.7 vs 363 ± 43.5 (P < .01), and TRHCO3 as mEq per 100 ml GFR was 2.09 ± 0.06 vs 2.53 ± 0.06 (P < .01). The data indicate that CT suppresses glucose and bicarbonate reabsorption together with that of sodium and as such assign to role for renal cyclic AMP in the r...

Changes in plasma volume and extracellular fluid volume after addition of prazosin to propranolol treatment in patients with hypertension.

In fifteen patients with hypertension, inadequately controlled during treatment with propranolol alone (mean dosage 333 mg/day), plasma volume (PV) and extracellular fluid volume (ECV) were determined. After addition of prazosin for 3 months (mean dosage 9 mg/day) there was a significant increase in PV and ECV, on average 8 and 5%, respectively. The decrease in supine blood pressure, systolic as well as diastolic, was very modest, on average 11 mmHg (SD +/- 12) and 4 mmHg (SD +/- 7), respectively. The changes in standing blood pressure were more pronounced. It is assumed that the expansion of PV and ECV contributes to the inadequate blood pressure response found in the present study.

Effects of phosphate depletion on acid-base status in dogs

Hyperchloremic acidosis may occur in patients with severe hypophosphatemia, including some with hyperparathyroidism. In experimental models of phosphate depletion, metabolic acidosis has not been a consistent feature. In some studies, arterial pH values have been normal, but have been associated with high rates of urinary bicarbonate loss. In other studies, metabolic acidosis has been observed associated with a decreased capacity for renal bicarbonate reabsorption. The present study was designed to examine the effects of both phosphate depletion upon systemic acid-base status in dogs and chronic hypophosphatemia upon renal bicarbonate reabsorption. Studies were performed upon three groups. All received a standard diet markedly diminished in phosphate content. Normal dogs (group I) received a dietary supplement of phosphate (31 m M/day). Group II dogs received no supplemental phosphate. Group III dogs were parathyroidectomized and also received a phosphate-deficient diet. Deprivation of dietary phosphate in groups II and III resulted in severe hypophosphatemia (Serum phosphate = 1.1 mg phosphorus/dl). Renal fractional phosphate reabsorption was increased significantly in both groups. Despite phosphate deprivation for up to 14 wk, arterial pH and bicarbonate values remained normal. Values for fasting urine pH and bicarbonate excretion were similar in the three groups. Renal bicarbonate conservation was normal in groups II and III as observed under fasting conditions. During bicarbonate infusion studies, patterns of bicarbonate reabsorption/glomerular filtration rate were obtained and maximal rates of renal bicarbonate reabsorption were assessed. To correct for possible differences ascribable to the effects of extracellular fluid volume expansion, the ratio of absolute bicarbonate/absolute sodium reabsorption was also examined. Over a wide range of plasma bicarbonate concentrations, no significant differences in this ratio were observed among the three groups. Maximal rates of renal bicarbonate reabsorption were similar in the three groups. The studies demonstrate that prolonged dietary phosphate deprivation in dogs, while resulting in severe hypophosphatemia, may be associated with the maintenance of normal plasma pH and bicarbonate values. Abnormal rates of urinary bicarbonate loss have not been observed. In the absence of metabolic acidosis, bicarbonate reabsorptive capacity and bicarbonate reabsorptive patterns are normal. The study suggests that other causes for the metabolic acidosis in severe phosphate depletion should be sought.

Indomethacin and diclofenac sodium increase sodium and water excretion after extracellular volume expansion in the rabbit

The renal effects of an acute extracellular fluid volume expansion (50 ml Ringer/kg body weight/60 min) were studied in aldosterone-treated (100 μg/kg), anesthetized rabbits with and without pretreatment with either indomethacin (3.0 mg/kg) or diclofenac sodium (3.0 mg/kg), two different inhibitors of renal prostaglandin (PG) biosynthesis. In controls (n = 7), the volume expansion increased urine flow from 1.5 ± 0.24 to 6.1 ± 0.5 (S.E.) ml/min/100 g kidney weight and sodium excretion from 0.15 ± 0.03 to 0.99 ± 0.10 mmol/min/100 g. PAH and insulin clearance increased by 42 and 58%, respectively, while plasma renin activity and urinary excretion of PGF 2α-like immunoreactivity were reduced (P < 0.05). In aninals pretreated with indomethacin (n = 6) or diclofenac sodium (n = 6), the diuresis and the natriuresis following volume expansion were significantly increased about two-fold over controls, whereas PAH and inulin clearance, plasma renin activity and hematocrit did not differ from controls. Both drugs were found to reduce urinary excretion of PGF 2α-like immunoreactivity by 75–95% throughout the experiment. The results indicate that diclofenac sodium, indomethacin and extracellular volume expansion enhance sodium and water excretion partly by suppression of a PG sensitive reabsorption process in the kidney.

Influence of Inhibitors of the Renin-Angiotensin System and the Renal Prostaglandins on Furosemide-induced Changes in Renal Blood Flow

The effects of inhibitors of the renin-angiotensin system and prostaglandin synthesis were used to study furosemide-induced changes in renal hemodynamics. Extracellular fluid volume expansion augmented the increase in renal blood flow to furosemide when compared to hydropenic animals. Indomethacin, a prostaglandin synthetase inhibitor, blunted the effect of furosemide in volume-expanded animals. Neither SQ 20,881, an angiotensin I converting enzyme inhibitor, nor 1-Sar-8-A1a-angiotensin II, an angiotensin II antagonist, modified the response to the diuretic. The initial transient decrease in renal blood flow seen following furosemide was not modified by volume expansion, indomethacin, SQ 20,881 or 1-Sar-8-A1a-angiotensin II.

Characterization of the renin-aldosterone system in decompensated cirrhosis.

SUMMARY' Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant central hypervolemia induced by water immersion to the neck (NI) produces a prompt and profound suppression of plasma renin (PRA) and plasma aldosterone (PA) without concomitant alterations in serum sodium and potassium concentrations. The NI model was used to assess the responsiveness of both PRA and PA in cirrhosis. Sixteen cirrhotic patients were studied twice while in balance on a 10 mEq sodium, 100 mEq potassium diet, under control conditions and during NI. The conditions of seated posture and time of day were identical. Plasma for PRA and PA was obtained at 30-minute intervals for 6 hours. NI produced profound suppression of PRA as early as 60 minutes with maximal suppression (70%) by 150 minutes (P < 0.005). Recovery from NI was associated with a prompt return to prestudy levels. PA was suppressed within 60 minutes with a maximal suppression of 59% by 240 minutes (P < 0.005) and a prompt return to prestudy levels during recovery. The suppression of PA paralleled that of PRA throughout the immersion period (P < 0.005). Although 15 of the 16 subjects manifested a significant suppression of PA, eight subjects manifested either a blunted or absent natriuretic response during NI. These data demonstrate that the elevated PRA and PA levels of cirrhosis are suppressed promptly and markedly in response to a standardized volume stimulus. The parallelism of changes in PRA and PA supports the importance of the renin-angiotensin axis in the control of volume-regulated changes in PA in cirrhotic man. Finally, our demonstration of the dissociation between the marked suppression of circulating PA and the absence of a natriuresis in eight of these subjects suggests strongly that aldosterone plays only a permissive role in relation to the impaired sodium excretion of cirrhosis. DESPITE documentation of excessive levels of plasma renin activity (PRA) and plasma aldosterone concentration (PA) in patients with decompensated alcoholic cirrhosis, the responsible mechanism or mechanisms remain controversial. 1 " 8 Furthermore, the responsiveness of PRA and PA to alterations of extracellular fluid volume and postural stimuli are uncertain and there is a recent report suggesting that PRA and PA are unaffected by extracellular fluid volume expansion in many cirrhotic patients. 4 The assessment of the responsiveness of PRA and PA to volume alteration has been confounded by the distinct hazard of infusing exogenous volume expanders in patients who already are markedly volume-expanded. Furthermore, sequential sampling of blood for kinetic assessment of PA produces a degree of volume contraction which, in and of itself, may perturb the experimental results. Since recent studies from our laboratory have demonstrated that the central hypervolemia induced by immersion produces a prompt and profound suppression of the renin-aldosterone system without concomitant alteration of plasma composition, 9 " 12 we undertook to char

Role of Cyclic AMP in the Natriuresis of Extracellular Fluid Volume Expansion in the Dog

1. The effect of extracellular volume expansion (ECVE) on renal production of cyclic AMP was evaluated in 19 thyroparathyroidectomized dogs. ECVE was produced by the infusion of Ringer bicarbonate solution at a rate of 2 ml min-1 kg-1 body weight; cyclic AMP was measured in plasma obtained from the aorta and renal vein and in the urine. 2. During the natriuresis of ECVE urinary excretion of cyclic AMP, the clearance of cyclic AMP, net nephrogenous cyclic AMP added both to urine and to the renal vein and hence total nephrogenous cyclic AMP increased significantly. 3. This rise in net production of cyclic AMP and a significant natriuresis by the kidney persisted for 60--90 min after discontinuation of active ECVE and return of renal plasma flow to normal. 4. The results support the notion that an increase in the production of cyclic AMP by the kidney may play a role in the natriuresis of ECVE.

Circulating inhibitor of sodium-potassium-activated adenosine triphosphatase after expansion of extracellular fluid volume in rats.

1. Serum was collected from normal rats and from rats volume-expanded with isotonic sodium chloride solution. 2. The serum was fractionated by gel filtration on Sephadex G-25 and each fraction was tested for inhibitory activity against sodium-potassium-activated adenosine triphosphatase prepared from rat kidney homogenate. 3. A single low-molecular-weight fraction, eluting after the salts and after exogenously added lysine-vasopressin, had significantly greater enzyme inhibitory activity when obtained from serum of volume-expanded animals than from control serum. 4. As this fraction has been shown in previous independent studies to contain a natriuretic factor, it may be concluded that one property of this factor is the ability to inhibit sodium-potassium-activated adenosine triphosphatase.

Effects of prostaglandin inhibition on intrarenal hemodynamics in acutely saline-loaded rats.

We studied the effect of inhibition of the prostaglandin (PG)-synthesizing enzyme system in female Sprague-Dawley rats following acute expansion of the extracellular fluid volume (ECV). In 57 conscious rats expansion of the ECV with isotonic saline corresponding to an increase in body weight of 10% was induced. Prior to ECV expansion 31 rats received indomethacin (10 mg/kg of body wt) by stomach tube. In six non-ECV-expanded rats indomethacin had no effect on glomerular filtration rate (GFR) and renal plasma flow (RPF). In ECV-expanded rats pretreated with indomethacin, GFR was unaltered but 125I-hippuran clearance decreased, and filtration fraction significantly increased. Intrarenal 86Rb distribution was similar in control and ECV-expanded rats. Indomethacin caused a slight increase in relative cortical 86 RB activity in non-ECV-expanded rats, but had no effect on intrarenal 86Rb distribution in ECV-expanded rats. No difference in intracortical glomerular perfusion was noted between control and ECV-expanded rats. In indomethacin-treated ECV-expanded rats an increase in relative inner cortical perfusion was observed. Absolute perfusion remained unaltered. Thus the decrease in total RPF was entirely due to decreased perfusion of outer cortical nephrons. Renal prostaglandins therefore may play a permissive role for physical factors to promote renal sodium excretion in acute ECV expansion via changes in intrarenal hemodynamics.

Renal response to infusion of isotonic Ringer-Locke solution: effect of hypophysectomy.

A comparison of the renal response to extracellular fluid volume expansion (5% body weight) was made between 25 normal and 25 chronically hypophysectomized rats. The extracellular fluid compartments averaged 25 ± 1% of body weight in both groups during control, fasted conditions. Extracellular fluid volume increased to 33 ± 1% in hypophysectomized and 34 ± 2% in normal rats during expansion, based on body weight. In addition, filtration fraction was similar in both normal and hypophysectomized rats during control (0·29 ± 0·03 and 0·26 ± 0·02 respectively) and infusion of Ringer–Locke solution (0·24 ± 0·05 and 0·27 ± 0·05 respectively). Thus our results cannot be explained by differences in the degree of expansion or failure to increase filtration in proportion to plasma flow. During infusion of isotonic Ringer–Locke solution, fractional water and sodium excretion both averaged 5·1% in normal rats and only 1·3% and 0·82% respectively in hypophysectomized rats. The ratio of single nephron to whole kidney filtration rate failed to increase as much in hypophysectomized compared with normal rats. Significant increases of fractional volume excretion occurred in both groups by the end of the accessible portion of the proximal tubule. However, fractional water reabsorption was depressed significantly more in normal (mean = 37%) than in hypophysectomized rats (mean = 19%). Fractional water reabsorption in distal tubules was similar in both groups during expansion. Arterial pressure was lower in hypophysectomized rats under control conditions, but showed similar changes during expansion compared with normal rats. Passage time decreased significantly in all groups after Ringer–Locke infusion, but remained prolonged in hypophysectomized rats in proximal and distal tubules. It is concluded that chronic hypophysectomy results in a less efficient renal excretion of volume and sodium chloride load. This inefficiency appears to be related in part to (1) failure of the proximal tubule to depress water reabsorption to a level equivalent to normal rats, and (2) failure to re-distribute flow to outer cortical glomeruli following extracellular fluid volume expansion in hypophysectomized rats.

The effect of small doses of antidiuretic hormone on renal excretion of sodium and water in saline loaded acutely hypophysectomized rats.

Small doses of vasopressin (200 micronU min-1 kg-1) did not influence the loss of ability of acutely hypophysectomized rats to react by natriuresis to the extracellular fluid volume expansion with saline, inspite of restoring their arterial blood pressure to normal. It is concluded that the level of antidiuretic hormone efficient enough to concentrate urine is not a decisive factor in the homeostatic mechanism promoting the 'volume' natriuresis.

Extravascular lung water after extracellular fluid volume expansion in dogs.

We have compared extravascular lung water after extracellular fluid volume expansion with that predicted from lung sucrose space measured in control dogs. In control lungs mean extravascular water:dry weight ratio was 3.81 +/- 0.16 (SD) (n = 5) and extravascular sucrose space/dry weight was 1.79 +/- 0.45 (n = 4). After acute expansion of extracellular fluid volume by 10% of body weight mean extravascular water:dry lung weight was 4.17 +/- 0.27 (m = 5), less than half the predicted increase to 4.63 +/- 0.19, suggesting some degree of protection. After 20% (n = 4), 30% (n = 2), and 40% (n = 1) expansion, no protection was demonstrated and there was considerable scatter of lung water at each infusion volume. When volume expansion increased pulmonary capillary intravascular forces (due to decreased protein osmotic pressure and increased hydrostatic pressure) by more than 20 cmH2O there was a linear increase in extravascular lung water with increasing intravascular forces. Three dogs did not conform to this relationship and had disproportionately large increases in lung water, possibly due to alveolar flooding.

Plasma aldosterone during extracellular fluid volume expansion in patients on regular haemodialysis

The influence of extracellular fluid volume expansion on the plasma aldosterone concentration (PAC) was investigated in five anephric and six non-nephrectomized patients on regular haemodialysis, and compared to a control group of four anephric and four non-nephrectomized patients. Plasma-renin activity, cortisol, Na+, and K+ were measured together with the PAC during the investigation. In anephric patients the PAC remained constant during the control period as well as during extracellular fluid volume expansion by infusion of 350 mmol of 20% mannitol. In the non-nephrectomized patients PAC diminished after mannitol infusion. The decline in PAC was correlated with the basal levels of PAC and the plasma renin activity. It is concluded that 5% extracellular fluid volume expansion has no direct influence on the regulation of PAC in patients without the renal renin-angiotensin system and that the regulation of PAC in anephric patients in the present investigation is probably mediated by changes in potassium and ACTH.

The role of the kidney in hypertension.

The role of the kidney in hypertension is reviewed in terms of sodium and water homeostasis, of the secretion of renin inappropriate to the state of sodium and water balance and of other renal humoral factors which might be implicated in the hypertensive process. Fundamental to the long-term maintenance of hypertension is an alteration in the relationship between renal perfusion pressure and the excretion of sodium and water. This alteration may be brought about as a result of renal structural damage, sympathetically mediated renal vasoconstriction or the action of renal or extrarenal hormones which modulate sodium and water excretion. When renin is secreted in excess of the prevailing level of sodium and water balance, the generated angiotensin contributes to the hypertension directly through peripheral and renal vasoconstriction. The level of blood pressure in two hypertensive patients with chronic renal failure was found to be highly correlated with the level of plasma renin activity as this was lowered by the administration of a beta-blocking drug. In rats deprived of sodium, renal artery constriction and contralateral nephrectomy was followed by hypertension without any elevation of plasma angiotensin and with a minimal expansion of plasma volume unaccompanied by expansion of extracellular fluid volume. The possible role of this small volume change and of other possible factors in producing hypertension is discussed. Studies in the nephrectomised rat confirmed eariler reports that renal medullayr auto-explants inhibited renoprival hypertension, but neither the identity nor mode of action of the medullary hypotensive factor were further clarified.

Failure of sodium restriction to abolish exaggerated natriuresis in poststreptococcal glomerulonephritis.

Exaggerated natriuresis in response to hypertonic saline infusion occurs with great regularity in patients with documented previous attacks of poststreptococcal glomerulonephritis. Five patients were studied before and after 1 week of dietary sodium restriction in order to examine the possibility that increased extracellular fluid volume might play a role in the response to acute saline infusion. Plasma renin activity (PRA) and PRA responsiveness to sodium depletion were normal, suggesting that extracellular fluid volume was not increased. In all patients, extracellular fluid volume decreased during sodium restriction, as judged by weight loss, cumulative negative sodium balance, small decreases in measured plasma volume, and appropriate increases of PRA and plasma aldosterone concentration. Hypertonic saline infusion provoked exaggerated natriuresis in all patients equally as well after dietary sodium restriction as before. Exaggerated natriuresis in poststreptococcal glomerulonephritis occurs without evidence of chronic expansion of extracellular fluid volume and is not affected by reduction of extracellular fluid volume.

High sodium-low potassium environment and hypertension

The high sodium-low potassium environment of civilized people, operating on a genetic substrate of susceptibility, is the cardinal factor in the genesis and perpetuation of “essential” hypertension. The noxious effects begin in childhood, when habits of excess salt consumption are acquired at the family table, and are perpetuated by continuing habit and by increasing use of convenience and snack foods with artificially high concentrations of sodium and low levels of potassium. Present methods of food preparation leach out the protective potassium. Extradietary sodium chloride is a condiment, not a requirement. Some primitive populations clearly preferred potassium chloride to sodium chloride. Chronic expansion of extracellular fluid volume induced by excess salt consumption causes the central and peripheral circulatory regulatory mechanisms to work at cross purposes, resulting in increased arterial pressure. The protective effect of potassium is dramatic and easily demonstrable in animals and man but its mechanism is not known. It cannot be entirely a direct effect on blood pressure because rats protected with extra potassium against a moderately high salt intake live much longer than control rats but have the same elevated blood pressures. In hypertension with a demonstrable “cause,” the high sodium-low potassium environment makes a bad matter worse. In nature, feral man and his forebears were not confronted with excessive sodium and deficient potassium; indeed, the reverse was the case. Evolution has provided powerful mechanisms for conserving sodium and eliminating potassium, but no efficient physiologic mechanisms for conserving potassium and eliminating excess sodium. Most laboratory animal “control” diets contain an amount of sodium that fully suppresses aldosterone secretion, and the same is true of the “average” diet of the American people. Inadequate attention to dietary sodium and potassium makes many studies in both animals and man of uncertain validity. Internally, essential hypertension is an exceedingly complex mosaic of physiologic interactions. Viewed from outside, it is a disorder for which genetic material sets the stage; excessive sodium precipitates it and perpetuates it. Extra salt makes all forms more rapidly progressive and accelerates the onset of terminal events; extra potassium is everywhere protective. When an entire population eats excessively of salt, hypertension will develop among those genetically susceptible, but epidemiologic studies of salt versus blood pressure will not show a relation of salt to hypertension. This is the saturation effect. Low sodium diets are therapeutically effective but generally regarded as an impossible or an unnecessary nuisance. Effective prevention programs must be instituted at as early an age as possible. The efficacy of a prophylactic/therapeutic low sodium-high potassium diet should be weighed against the uncertain hazards of a lifetime of pill taking.

Effects of extracellular volume expansion on the tubular reabsorption of glucose. A microinjection study.

Clearance and intratubular injections of (14C) glucose were performed in glucose loaded rats, during control (C) and extracellular fluid volume expansion (VE) to 10% of body weight. VE resulted in a significant decrease in hematocrit from 47.50 +/- 1.06 to 38.80 +/- 1.14% and plasma protein from 6.23 +/- 0.25 to 4.13 +/- 0.21 gm/100 ml. Glomerular filtration rate (GFR) increased by 51% from 1.06 +/- 0.07 to 1.60 +/- 0.35 ml/min. Fractional excretion of sodium increased significantly from 0.42 +/- 0.07 to 12.58 +/- 1.25%. Maximal glucose reabsorption (TmG) was unchanged from 3.47 +/- 0.42 to 3.29 +/- 0.41 mg/min. However, TmG/GFR decreased significantly from 3.14 +/- 0.22 to 1.94 +/- 0.21 mg/ml GFR. As compared to C, VE resulted in a significant increase in (14C) glucose recovery after injection into the early and late proximal tubules, from 63 +/- 3 to 81 +/- 2% to 88 +/- 1% respectively. After distal tubular injections (14C) glucose recovery was complete in both C and VE; early distal injection 97 +/- 1 vs 98 +/- 1%, late distal injection 98 +/- 1 vs 99 +/- 1%. These results indicate an inhibitory effect of VE on fractional glucose reabsorption in the superficial nephron. There is no evidence for glucose reabsorption in the superficial distal nephron during C and VE.

Effect of prostaglandin inhibition on renal response to volume expansion in dog

A prostaglandin (Pg) has been proposed as a “natriuretic hormone” effecting the natriuresis observed with extracellular fluid volume expansion. Dogs were volume expanded under chloralose anesthesia by equilibrating the animal's blood with the saline expanding volume outside of the body prior to infusion, in order to avoid hemodilution during expansion. The massive natriuresis associated with expansion was not significantly affected by preloading injection of indomethacin (5–10 mg/kg) to depress prostaglandin synthesis. Consistent with studies by others, a rise in filtration fraction was observed in 4 of 5 experiments with indomethacin but not in its absence. The results do not support the concept that the hypothetical natriuretic hormone is a Pg or is dependent upon a Pg for its synthesis or release. The data, moreover, constitute further evidence that the nutriuresis of acute volume expansion does not depend upon decreased colloid osmotic pressure in the renal peritubular capillaries. Urinary Pg F 2αexcretion was depressed by indomethacin but was unaffected by expansion. Expansion was associated with an unexplained 10 percent decrease in plasma potassium concentration.