Is urinary flow rate a major regulator of prostaglandin E excretion in man?

Urinary PGE₂ excretion is enhanced in several polyuric states in man suggesting that PGE₂ synthesis could be a mediator of diuresis. To explore the alternate hypothesis that polyuria is the cause of the increased PGE₂ excretion, we increased urine flow rate by intravenous administration of dextrose and water with different magnesium, calcium and potassium solutions in four normal males. Urinary PGE excretion rose in parallel with urine volume (r = 0.65 p < 0.01) independently of the electrolyte solution. To determine the effects of chronic alterations in water balance in 5 female subjects, we sequentially regulated oral water intake to induce 1, 2, 4 and 8 liters of urine volume/day. During low (40 mEq) sodium diets, PGE increased from 540 ± 50 to 4880 ± 1240 ng/d with increasing urinary volume (r = 0.81, p < 7.01). Similarly, for 200 mEq sodium intake PGE paralleled urinary volume (from 630 ± 100 to 4740 ± 800 ng/d, r = 0.61, p <0.01). In vitro sample dilution studies demonstrated no interference from method blank, and the addition of thin layer chromatography prior to Sephadex chromatography failed to alter assay measurements. We conclude that extreme increases in urinary flow rate may directly enhance PGE excretion in man.     

Urinary prostaglandin E excretion: Effect of chronic alterations in sodium intake and inhibition of prostaglandin synthesis in the rabbit

On the basis of acute experiments in animals, a role for prostaglandin E (PGE) in the regulation of urinary sodium excretion has been suggested. Limited information is available, however, concerning the possible role of PGE in chronic adjustments to sodium intake. These studies were designed to determine whether chronic changes in sodium balance would modify renal PGE excretion and whether partial inhibition of prostaglandin synthesis would after the ability of the kidney to adjust to an alteration in sodium intake. Thus, we measured sodium and PGE excretion in rabbits on chronic high and low salt diets before and after inhibition of prostaglandin synthesis with indomethacin or meclofenamate. Although the alterations in salt intake resulted in large changes in sodium excretion there was no significant change in urinary PGE excretion. After administration of either indomethacin or meclofenamate for several days there was a significant fall in PGE excretion, but no significant change in sodium excretion. These results suggest that in the rabbit 1) chronic changes in sodium excretion can occur without modifying PGE excretion (and presumably renal PGE synthesis) and 2) inhibition of PGE synthesis does not impair the kidney's ability to adjust to a chronic high or low sodium intake.     

Evidence from a dual action of converting enzyme inhibitor on blood pressure in normal man

We studied the effect of a converting enzyme inhibitor (CEI), Captopril SQ 14,225 50 mg p.o. in eight supine normal subjects under a high sodium (150 meq/d) and low sodium (25 mEq/d) diet. On high sodium, plasma renin (PRA) and aldosterone were basal and Saralasin did not lower mean blood pressure. However, CEI induced an 11.4±3.2 mm fall in blood pressure (p<0.02) and either indomethacin 50 mg or ibuprofen 800 mg (PI), when given simultaneously on another day, abolished the blood pressure response (2.5±0.9 mm Hg, p>0.5). In contrast, on a low salt diet where renin was increased, CEI induced a drop in blood pressure which was not significantly altered by PI (12.8±1.1 vs. 10.0±3.1 mm Hg, p>0.5). CEI increased plasma renin on both diets (1.7±0.5 to 3.5±0.8 and 2.8±0.6 to 12.5±3.1 ng/ml/hr respectively both p<0.05). Aldosterone did not change (high Na⁺) or fell (low Na⁺). Inhibition of prostaglandin synthesis did not significantly block the renin rise from CEI suggesting that the direct angiotensin II negative feedback is relatively independent of acute prostaglandin release. Our studies suggest that CEI has a dual hypotensive action. In a low renin state, the hypotensive action appears to be mediated through vascular prostaglandins.     

Effects of inhibition of prostaglandin-synthesis on renal electrolyte excretion and concentrating ability in healthy man

In five healthy subjects inhibition of prostaglandin (PG)-synthesis with indomethacin did not significantly alter glomerular filtration, urinary flow rate or sodium and potassium excretion during control urine collection periods or i.v. hypertonic saline infusion. Saline administration was accompanied by a fall in urinary PGE₂-excretion from 0.58±0.14 to 0.26±0.09 ng/min (p < 0.05). While indomethacin had no effect on basal urinary osmolality (I_osm),renal concentrating ability following hypertonic saline or i.v. administration of 100 mU lysine-vasopressin significantly increased in the presence of indomethacin with U_osm rising from 805±25 to 970±53 mosm/L (p < 0.01)and from 839±47 to 996±62 mosm/L (p < 0.01),resp. Since this was not accompanied by respective changes in urinary excretion of cyclic adenosine monophosphate (cAMP) mechanisms other than PG-antagonism of vasopressin, such as decreased medullary washout of solute, may contribute to enhanced renal concentrating ability following inhibition of PG-synthesis with indomethacin.     

Effects of a nonperssor analogue of vasopressin on plasma renin activity and salt and water excretion in water-loaded,anesthetized dogs

The object of this study was to determine the importance of vasoconstrictor activity in the suppression of renin secretion by vasopressin. Arginine vasopressin (AVP) (0.05 and 0.1 ng/kg/min) and a nonpressor analogue of vasopressin, 1-deamino-[4-threonine, 8-D-arginine]-vasopressin (dTDAVP) (0.01 and 0.05 ng/kg/min), were infused intravenously in anesthetized hypophysectomized dogs. Neither dTDAVP nor AVP influenced arterial pressure or heart rate but both suppressed plasma renin activity. Infusion of dTDAVP at 0.01 and 0.05 ng/kg/min suppressed plasma renin activity to 86±4% (p<0.05) and 63±6% (p<0.01) of the control values respectively. Infusion of AVP at 0.05 and 0.1 ng/kg/min suppressed plasma renin activity to 60±8% (p<0.01) and 59±12% (p<0.05) of the central values respectively. dTDAVP and AVP both produced significant increases in sodium excretion. These data demonstrate that vasoconstrictor activity is not required for the effects of vasopressin on renin secretion and sodium excretion.     

Role of volume and prostaglandin synthesis in the suppression of renin by saline in the rat

To evaluate the contribution of plasma volume expansion per se on acute inhibition of renin release by sodium chloride infusion, renin responses to comparable plasma volume expansion with intravenous infusions of sodium chloride, sodium bicarbonate, or albumin were studied in separate groups of sodium chloride-depleted rats. In addition, urinary prostaglandin E2 (PGE2) excretion rate was compared in the saline- and sodium bicarbonate-infused animals to evaluate the relationship between acute changes in renin release and intrarenal PGE2 synthesis. All three groups were plasma volume-expanded by approximately 55%. Plasma renin activity (PRA) decreased in response to saline (12.3 +/- 1.0 to 6.7 +/- 0.7 ng AI/ml/hr; P less than 0.01) whereas PRA did not change with sodium bicarbonate (11.3 +/- 1.4 to 10.2 +/- 1.5) or albumin (9.9 +/- 0.7 to 8.2 +/- 1.0). The rate of PGE2 excretion was not changed by either saline (72.2 +/- 13.1 to 72.3 +/- 18.7 pg/min) or sodium bicarbonate infusion (70.7 +/- 8.8 to 64.9 +/- 7.0). These results support the hypothesis that acute suppression of PRA by infusion of saline is not dependent upon volume expansion per se. In confirmation of earlier observations, inhibition of renin release by sodium chloride was related to chloride. Finally, the results suggest that the renal tubular mechanism for inhibition of renin release by sodium chloride is not related to overall changes in renal PGE2 synthesis in the rat.     

The effect of angiotensin II and indomethacin on immunoreactive prostaglandin “A” levels in man

The effect of angiotensin II on peripheral levels of immunoreactive prostaglandin A₂ (IR-PGA) was determined in 17 normal male volunteers. IR-PGA rose from 338 ± 65 (SE) pg/ml to 635 ± 142 in response to pressor infusions of angiotensin II (p <0.05 on paired analysis). This increase was not observed when indomethacin, 75 mg p.o., was given to 8 patients two hours prior to a repeat infusion. Five patients of the original group were placed on a low sodium diet (10–20 mEq). The response to angiotensin was now exaggerated (278 ±52 pg/ml to 916 ± 284). These five patients were kept on a low sodium intake and given indomethacin 50 mg p.o. q 6 hourly for 4 days. There was no significant rise with angiotensin infusion (106 ± 31 pg/ml to 120 ± 70). Pressor infusions of angiotensin II raise peripheral levels of IR-PGA, and this response is exaggerated by a low sodium diet and blocked by either acute or chronic indomethacin administration. This data supports the concept that vasodilatory prostaglandins may be released by endogenous angiotensin and thus provide a dynamic antagonism to the renin angiotensin system in man.     

Alpha melanocyte stimulating hormone inhibits prolactin secretion in fetal and infant lambs

The intravenous administration of αMSH (25 μg/kg) to 11 lambs (3 to 29 days of age) suppressed plasma PRL by 15 minutes. The mean basal concentration was 15.3 ± 2.9 ng/ml and the mean nadir was 4.9 ± 0.8 ng/ml (p<0.01). In chronically catheterized fetuses (128–140 days), intravenous administration of αMSH (25 μg/kg) decreased basal PRL levels (89.6 ± 12.4 ng/ml) significantly at 15–30 minutes to levels of 74.3 ± 11.4 ng/ml (p<.01). The degree of suppression of basal PRL levels was less in fetusus (76.9 ± 4.1%) than that induced in the neonates (40.5 ± 7.1%). In younger fetuses <120 days in whom basal PRL levels are low (3.0 ± 2.1 ng/ml), administration of αMSH was without effect. Plasma GH concentrations were not altered by administration of αMSH. The suppression of PRL secretion by αMSH administration could result from increased release of hypothalamic dopamine or be a direct effect on secretion of prolactin by the pituitary.     

Urinary prostaglandin and kallikrein excretion are not flow dependent in the rat

To study the relationship between urine flow, urinary prostaglandin (PG) and kallikrein excretion in the rat high urine flow was induced in hydropenic Long-Evans rats by either hypotonic volume expansion or with manniitol or with furosemide. PGE, excretion remained unchanged during hypotonic volume expansion (134.5 ± 29.7 before and 153.0 ± 48.9 pg/min after) while it decreased significantly with mannitol (from 166.3 ± 32.4 to 45.2 ± 8.2 pg/min, p<0.01) and with furosemide (from 170.0 ± 20.4 to 29.5 ± 5.3 pg/min, p<0.001). PGF_2α excretion rates were slightly reduced following all three interventions. Urinary kallikrein excretion remained unchanged in all three groups of animals. It is concluded that, in contrast to human and dogs in the rat urine flow and urinary PG excretion are not interlinked.     

Comparison of the natriuresis and chlorures is associated with glomerular hyperfiltration induced by atrial natriuretic factor or glucagon

The impact on renal sodium chloride reabsorption of an acute increase in glomerular filtration rate (GFR) induced by atrial natriuretic factor (ANF) or glucagon was examined in the conscious rat. These hormones have no direct effect on proximal solute transport and have opposite effects on distal transport. ANF and glucagon increased GFR to a comparable extent (2.0 ± 0.2 to 3.5 ± 0.4 ml/min, p<0.01, and 1.9 ± 0.1 to 3.3 ± 0.1 ml/min, p<0.001, respectively). While most (95–97%) of the increment in filtered sodium chloride was reabsorbed, a small portion (3–5%) escaped tubular reabsorption. Absolute sodium and chloride urinary excretion rates increased similarly in response to each hormone, by two- to three-fold. Slightly imperfect load-dependent sodium chloride reabsorptive response by the nephron, despite opposite direct effects on distal nephron transport, may account for the observed natriuresis and chloruresis associated with the acute glomerular hyperfiltration induced by ANF or glucagon administration.     

Redistribution of intrarenal blood flow following adh administration: Lack of inhibition by blockade of prostaglandin cyclooxygenase

The effect of prostaglandin synthesis inhibition on the redistribution of renal cortical blood flow in response to antidiuretic hormone (ADH) was examined using radioactive microspheres in water loaded, thiopental-anesthetized dogs. Microsphere injections were made during a control and an ADH infusion period (0.35 mU/kg/min following a 20 mU/kg bolus) both before and after indomethacin pretreatment (8 mg/kg intravenously). Urinary prostaglandin E₂ (PGE₂) excretion in each period was measured by gas chromatography-mass spectrometry. ADH caused a marked redistribution of flow toward inner cortical zones from 19±1 to 25±2 ml/min (mean^± SE, p < 0.01). Fractional flow to inner zones was also significantly increased. Indomethacin pretreatment had no effect on the ADH-induced redistribution (17±2 vs. 24±2 ml/min, p < 0.01), although urinary PGE₂ excretion was suppressed by indomethacin by 60%. It is concluded that prostaglandins do not mediate the redistribution of intrarenal blood flow accompanying ADH administration.     

Plasma immunoreactive atrial natriuretic peptide and changes in dietary sodium intake in man

Plasma levels of immunoreactive atrial natriuretic peptides (IrANP) have been measured in 8 normotensive subjects during alterations in dietary sodium intake. Subjects were studied on their normal sodium intake (2 days) then on a low sodium intake (7 days, 10 mmols Na+/day) and subsequently on a high sodium intake (14 days, 350 mmols Na+/day with the diets being given in a fixed order. Plasma levels (mean +/- S.E.M.) of IrANP on a normal sodium diet were 7.3 +/- 0.9 pg/ml; 4.5 +/- 0.8 on the 7th day of a low sodium intake and 10.8 +/- 1.3; 16.6 +/- 3.3; 15.5 +/- 4.2; 15.6 +/- 2.3 pg/ml respectively or the 1st, 3rd, 10th and 14th day on the high sodium intake. Changes in plasma IrANP were closely associated with changes in urinary sodium excretion. These results suggest that in normal subjects the atrial natriuretic peptides may play an important role in the adaptation to increases in dietary sodium intake both on a short and on a longer term basis.     

Mechanism for the increase in plasma renin activity by pentobarbital anesthesia

The mechanism by which pentobarbital anesthesia causes increases in plasma renin activity (PRA) was examined in dogs infused with either propranolol or indomethacin, an inhibitor of prostaglandin synthetase. Infusion of propranolol at 1 mg/kg, (I.V.) followed by 0.6–0.7 mg/kg/hr decreased PRA from 6.98±2.49 ng/m1/hr during control periods to 1.58±0.79 ng/m1/hr 30 minutes after the injection of propranolol (P<0.025). Subsequent induction of anesthesia with sodium pentobarbital caused PRA to rise to 3.87±0.93 ng/m1/hr in 30 minutes. (P<0.01). Plasma potassium concentration decreased from 4.6±0.2 mEq/L to reach 4.0±0.1 mEq/L 30 minutes after induction of anesthesia (P<0.005). Infusion of indomethacin at 5 mg/kg, (I.V.) followed by 1.5 ? 3.1 mg/kg/hr into conscious dogs did not decrease PRA. In contrast to the report by Montgomery et al (Fed. Proc. 36: 989, 1977), we found that the increase in PRA after pentobarbital anesthesia could not be blocked by indomethacin. PRA was 5.3±1.2 ng/m1/hr(M ± SEM) during control periods and was 4.7±1.4 ng/m1/hr 30 minutes after the infusion of indomethacin (P<0.1). PRA increased to 10.9±2.3 ng/m1/hr, 9.2±2.2 ng/m1/hr, and 7.7±1.7 ng/m1/hr at 5, 15 and 30 minutes, respectively, after the administration of pentobarbital (P<0.005, P<0.025, P<0.05). PRA declined to 4.2±1.3 ng/m1/hr 60 minutes after pentobarbital anesthesia (P<0.1). It is concluded that the mechanism by which pentobarbital causes increases in PRA is independent of prostaglandins.     

Role of substance P in water homeostasis.

The effect of the naturally occurring peptide substance P on release of antidiuretic hormone (ADH) was studied in anesthetized dogs. Intravenous infusions of substance P in doses of 0.5, 5.0, and 50 ng/kg/min increased plasma concentrations of ADH in a dose-related fashion. At the two low doses, this increase occured in the absence of changes in urine volume, sodium excretion, free water clearance, and urinary cyclic AMP excretion. In addition, when substance P was administered in a concentration of 0.5 ng/kg/min, plasma levels of ADH were increased even though blood pressure did not change, suggesting that substance P may release antidiuretic hormone by a direct mechanism. Intrarenal infusions at a rate of 0.5 and 5 ng/kg/min caused dose-related decreases in free water clearance and significant increases in urinary cyclic AMP excretion. These data suggest that substabce P may play an important role in the regulation of water balance.     

Increased excretion of bile acids by genetically hyperlipoproteinemic Zucker rat

Fecal excretion of neutral sterols and bile acids was measured in age-matched hyperlipoproteinemic Zucker obese rats and their lean litter mates. The bile acid excretion (mg/day ± SEM) in Zucker rats was significantly higher (p<0.01) when compared to lean controls (Zucker obese rats 41.68 ± 2.86; lean controls 29.85 ± 1.50). Neutral sterol excretion in both the groups of rats was similar. Total fecal steroid excretion (mg/day ± SEM) in Zucker rats was significantly higher (p<0.01) than in lean controls (Zucker obese rats 52.33 ± 3.50; lean controls 39.23 ± 2.16. The Zucker rat thus mimics the increased bile acid excretion noted previously in human Type IV hyperlipoproteinemia and could serve as an ideal animal model for studying the interrelationship between bile acid excretion and very low density lipoprotein metabolism.     

Further research on the role of prostanoids in controlling renal function in humans in normal potassium balance and acute experimental potassium depletion. I: Studies of normal potassium balance. Effects of indomethacin

The renal function was studied by clearance (cl.) method during hypotonic polyuria (oral water load followed by 5% dextrose solution infusion) and successive relative antidiuresis induced by lysine-8-vasopressin (LVP) administration (5 microU in bolo followed by continuous infusion at a rate of 0.04 microU/min). Four 15 min and two 60 min clearance (cl.) periods were performed during hypotonic polyuria and antidiuresis, respectively. Glomerular filtration rate was estimated by creatinine cl.; the osmotic cl. (Cosm, CH2O), the absolute and fractional excretions of water, sodium, potassium and chloride were determined by usual methods. The urinary PGE2, 6-keto-PGF1 alpha and TxB2 concentrations were determined by RIA method. Fourteen healthy women submitted to a normal sodium and potassium daily intake were studied; in 6 of them paired studies in absence and in presence of indomethacin (100 mg, i.m.), respectively, were performed. LVP induced a significant reduction of creatinine cl., urinary flow rate and of prostanoid excretion. In hypotonic polyuria, indomethacin significantly reduced the creatinine cl. and the diuretic response to the water load; moreover the urinary PGE2 and 6-keto-PGF1 alpha excretions were significantly lower (85.6 +/- 1.9% and 37.7 +/- 3.2%) while the reduction of urinary TxB2 excretion was not significant (34.4 +/- 13%). Indomethacin did not affect significantly the LVP renal effects in normal potassium balance.     

Hypercalcemia in association with a Leydig cell tumor in the rat: A model for tumor-induced hypercalcemia in man

The etiology of tumor-induced hypercalcemia was investigated in a transplantable Leydig cell tumor of the Fischer rat. In this model, serum calcium rose from a baseline of 10.4 ± 0.3 m mg/dl to 12.5 ± 0.4 mg/dl at day 10 and 16.4 ± 1.3 mg/dl (p<0.001) at day 13 post transplant. Urinary calcium also increased from 1.52 ± 0.17 mg/d to 3.52 ± 0.72 mg/d (Day 12, p<0.01). Serum phosphate decreased from a baseline of 7.5 ± 0.3 mg/dl to 5.5 ± 0.6 mg/dl at day 13 (p<0.05). At day 13 serum immunoreactive parathyroid hormone levels fell 76% from baseline (p<0.01). Calcitonin increased from 59 ± 2 pg/ml to 88 ± 9 pg/ml (p<0.01). The plasma prostaglandin E metabolite, 13, 14-dihydro-15-keto-PGE₂ increased from 407 ± 103 pg/dl to 647 ± 62 pg/ml (p<0.05) and the active Vit D compound 1, 25(OH)₂D increased from 94.8 ± 5.2 pg/ml to 162.3 ± 11.8 pg/ml (p<0.01). Urinary cyclic AMP did not decrease in parallel with the parathyroid hormone level and, in fact, increased from 146 ± 3 nmol/d to 172 ± 27 nmol/d (NS). Administration of the cyclooxygenase inhibitor indomethacin (20 mg/Kg/d) or hydrocortisone (50 mg/Kg/d) did not prevent the development of hypercalcemia. This model is similar to many patients with humoral hypercalcemia of malignancy who demonstrate suppression of parathyroid hormone with elevated urinary cyclic AMP excretion and may prove useful in the understanding of the responsible mechanisms.     

Effects of substance P on renin release and renal function in anesthetized dogs.

Substance P (SP), a naturally occuring undecapeptide with hypotensive, vasodilatory and smooth muscle stimulating properties, was infused intravenously or intrarenally into anesthetized dogs. Infusions of SP intravenously suppressed renin secretion rate (RSR) from 204±45 to 52±18 ng/min (p < 0.02) at an infusion rate of 0.5 ng/kg/min, and to 50±22 ng/min (p < 0.05) at 5 ng/kg/min. When the concentration of SP was further increased to 50 ng/kg/min, RSR increased to a level above the control value (728±81, p < 0.01). Intrarenal infusion of SP produced similar changes in renin release. At infusion rates of 0.5 ng/kg/min and 5 ng/kg/min, RSR was suppressed from 145±18 to 56±18 ng/min (p < 0.05) and to 26±8 ng/min (p < 0.01) respectively. At 50 ng/kg/min, RSR increased to 251±59 (p > 0.1). Both intravenous and intrarenal administration of the peptide significantly lowered arterial blood pressure at the highest two doses. Intrarenal infusion of SP resulted in a significant dose-related increase in urine volume, sodium and potassium excretion, and renal blood flow. In contrast, intravenous infusions did not alter these parameters. Thus SP suppresses renin release in the presence and in the absence of diuresis, natriuresis, and vasodilation.     

Metabolic Differences in Response to a High-Fat vs. a High-Carbohydrate Diet

Energy expenditure was measured in a group of 7 subjects who received two isocaloric isonitrogenous diets for a period of 9–21 days with a 4–10-day break between diets. Diet 1 was a high-fat diet (83.5 ± 3.6% of total energy). Diet 2 was a high carbohydrate diet (83.1 ± 3.7% of total energy). Resting and postprandial resting metabolic rate were measured by open circuit indirect calorimetry 2–4 times during each metabolic period. Total energy expenditure (TEE) was measured by the doubly labeled water method over an 8–13-day period. The respiratory quotient was measured 2–4 hours after a meal during each metabolic period for the calculation of total energy expenditure by the doubly labeled water method. Levels of total T₃ (TT₃), T₃ uptake, free thyroid index and T₄ were measured at the end of each metabolic period. No significant changes in resting metabolic rate (RMR) were apparent on the two diets (1567 ± 426 kcal/d high-fat diet and 1503 ± 412 kcal/d high-carbohydrate diet n=7, p<0.15). Total energy expenditure measured in 5 subjects was significantly higher during the high-carbohydrate phase of the diet (2443 ± 422 vs. 2078 ± 482 kcal/d p<0.05). Activity estimated from TEE/RMR was greater on the high-carbohydrate diet but only approached statistical significance (p<0.06). Total T₃ was significantly lower and free thyroid index and T₃ uptake were significantly higher at the end of the high fat diet in comparison to the high-carbohydrate diet. These data suggest that individual tolerance to a high-fat diet varies considerably and may significantly lower TEE by changing levels of physical activity. The explanation for changes in thyroid hormone levels independent of changes in metabolic rate remains unclear.     

Urinary excretion of AQP2 and ENaC in autosomal dominant polycystic kidney disease during basal conditions and after a hypertonic saline infusion

Renal handling of sodium and water is abnormal in chronic kidney diseases. To study the function and regulation of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in autosomal dominant polycystic kidney disease (ADPKD), we measured urinary excretion of AQP2 (u-AQP2), the β-subunit of ENaC (u-ENaC(β)), cAMP (u-cAMP), and prostaglandin E(2) (u-PGE(2)); free water clearance (C(H2O)); fractional sodium excretion (FE(Na)); and plasma vasopressin (p-AVP), renin (p-Renin), angiotensin II (p-ANG II), aldosterone (p-Aldo), and atrial and brain natriuretic peptide (p-ANP, p-BNP) in patients with ADPKD and healthy controls during 24-h urine collection and after hypertonic saline infusion during high sodium intake (HS; 300 mmol sodium/day) and low sodium intake (LS; 30 mmol sodium/day). No difference in u-AQP2, u-ENaC(β), u-cAMP, u-PGE(2), C(H2O), and vasoactive hormones was found between patients and controls at baseline, but during HS the patients had higher FE(Na). The saline caused higher increases in FE(Na) in patients than controls during LS, but the changes in u-ENaC(β), p-Aldo, p-ANP, p-BNP, p-Renin, and p-ANG II were similar. Higher increases in u-AQP2 and p-AVP were seen in patients during both diets. In conclusion, u-AQP2 and u-ENaC(β) were comparable in patients with ADPKD and controls at baseline. In ADPKD, the larger increase in u-AQP2 and p-AVP in response to saline could reflect an abnormal water absorption in the distal nephron. During LS, the larger increase in FE(Na) in response to saline could reflect a defective renal sodium retaining capacity in ADPKD, unrelated to changes in u-ENaC(β).