Cl Excretion Research Articles

Randomized controlled trial of colestipol in antibiotic-associated colitis

Thirty-eight patients with severe antibiotic-associated postoperative diarrhoea were entered into a randomized controlled trial to compare colestipol (an ion exchange resin) in 17 patients with placebo (sherbet) in 21 patients. Clostridium difficile or its toxin was present before treatment in 12 of the colestipol group, compared with only 5 in the placebo group. Because of the low incidence of Cl. difficile or its toxin, the placebo group data from 22 patients receiving placebo in a previous trial (9 of whom had Cl. difficile or toxin) were included for comparison. Neither colestipol nor placebo had any influence on the faecal excretion of Cl. difficile or its toxin. Colestipol was clinically no better than placebo. In view of the persistent faecal excretion of Cl. difficile toxin, ion exchange resins cannot be recommended for the treatment of antibiotic-associated colitis.

Influence of Sodium Valproate on Sodium and Chloride Urinary Excretion in Rats, Gender Differences

Evidence exists indicating that sodium valproate (VPA) increases diuresis in rats. The chloriuretic and natriuretic effect of VPA has not previously been investigated, so the aim of the present study was to define the peculiarities of 24-hour urinary sodium (Na) and chloride (Cl) excretion in young adult Wistar rats of both genders, and to evaluate the effects of VPA. 24-Hour urinary Na, Cl, creatinine and pH levels were measured in 28 control intact Wistar rats and 26 Wistar rats after a single intragastric administration of 300 mg/kg VPA. After VPA administration, 24-hour diuresis and 24-hour diuresis per 100 g of body weight were significantly higher in VPA rats of both genders. 24-Hour urine Na and Cl excretion were significantly higher in VPA male and VPA female rats than in gender-matched controls. The 24-hour urinary Cl excretion was found to be significantly higher in VPA male than in VPA female rats. The study data show that VPA, alongside the diuretic effect, enhances Na and Cl excretion with urine. The 24-hour chloriuretic response to VPA in male rats was significantly higher than in female rats. The mechanism of such a gender-related effect is not yet clear.

Impact of genetic polymorphisms in the gene coding for sodium potassium dichloride cotransporter (NKCC2) and serum glucocorticoid kinase (SGK1) for pharmacodynamics of furosemide

Background /Aims We were interested whether the known inter-individual variability in furosemide effects might be related with genetic polymorphisms in the sodium potassium dichloride cotransporter (NKCC2) and in serum and glucocorticoid regulated kinase (SGK1) which regulates NKCC2. Methods In an open-label single dose study 93 healthy male volunteers received a single dose of 80 mg furosemide. Urine volume, sodium, chloride, potassium and calcium excretion was measured in 9 intervals between 0 and 24 hours after drug administration. Results A total of 10 informative polymorphisms in the NKCC2 gene were analyzed but none of them was significantly associated with the furosemide effects. However, one intronically localized guanine/deletion (G/del) polymorphism in the SGK1 gene was associated with Na, Cl, K, and Ca urinary excretion. Na excretion in the first 3 hours after furosemide was 198, 247, and 273 mmol in G/G, G/del and del/del, respectively (p=0.002, ANOVA). This genotype-related difference was also seen in the cumulative 24-hour urine. Correspondingly, Cl excretion was also correlated with the SGK1 polymorphism (p= 0.001 for the 3h interval) and there were also differences in K and Ca excretion. We did however not observe significant influences on the urine volumes. Conclusions The finding with SKG1 might have great medical relevance but requires further confirmation because of the explorative nature of our investigation. Clinical Pharmacology & Therapeutics (2005) 77, P57–P57; doi: 10.1016/j.clpt.2004.12.107

A Case of Gitelman's Syndrome with Short Stature

We report the case of an 8-yr-old girl with short stature. Her height was -2.65 SD and blood examination revealed hypokalemia (2.9 mEq/l), hypomagnesaemia, hypocalsiuria (Ca/Cr=0.0039) and metabolic alkalosis (pH 7.454, HCO3- 24.9 mmol/l). For differential diagnosis between Gitelman's syndrome (GS) and Bartter syndrome (BS), we performed the loop diuretic furosemide (FUR) test and hydrochlorothiazide (HCT) double dose (2 and 4 mg/kg) test. Even the higher dose of HCT induced significantly lower increase of urinary Na and Cl excretions than the FUR. Growth hormone (GH) secretion tests (insulin and arginine) revealed GH deficiency. In addition to growth hormone injection, administration of Mg and spironolactone was started. After the replacement therapy started, the girl's height gain was improved (9.7 cm/yr) and her serum potassium became within the reference range. One year after GH replacement therapy was performed and GH replacement therapy was discontinued for two months, and GH secretion tests (insulin and arginine) showed GH deficiency again. We discussed previous reports of the clinical signs and test results of GS with regard to the relation between hypokalemia, hypomagnesemia and short stature.

Dietary cation-anion difference effects on performance and acid-base status of lactating dairy cows: a meta-analysis.

A meta-analysis was conducted to examine potential empirical relationships between dietary cation-anion difference (DCAD) (Na + K - Cl) and the response of lactating dairy cows. The database was developed from 12 studies published between 1984 and 1997 that included a total of 17 trials, 69 dietary treatments, and 230 cows. Results indicated that DCAD affected performance of lactating dairy cows. Maximum milk yield and feed intake were reached when DCAD was 34 and 40 meq/100 g of feed dry matter, respectively. Blood pH and HCO3 concentrations increased with DCAD, indicating an improved acid-base balance of lactating dairy cows. Changes in urinary pH and urinary excretion of Na, K, and Cl were consistent with varying DCAD, thus dietary acidity or alkalinity. The effects of DCAD were likely mediated via modification of acid-base status in the cows.

Role of P-glycoprotein in pharmacokinetics and drug interactions of digoxin and β-methyldigoxin in rats

Digoxin and beta-methyldigoxin were evaluated pharmacokinetically in terms of P-glycoprotein (P-gp)-mediated drug interactions in rats. Evaluation was made by measuring the effects of a potent P-gp inhibitor (verapamil, cyclosporin A) on in vitro efflux transport of these compounds across the everted small intestine, on in situ absorption from the small intestine, and on in vivo total plasma clearance (CL(total)) as well as biliary and urinary excretions after intravenous administration. Both the intestinal efflux transport and absorption of beta-methyldigoxin were approximately 1.5-fold greater than those of digoxin, probably due to its higher lipophilicity. Addition of verapamil (300 microM) significantly decreased the intestinal efflux transport and increased the intestinal absorption of digoxin. In contrast, the influence of verapamil on beta-methyldigoxin was small. Intravenous cyclosporin A (30 mg/kg) significantly decreased in vivo CL(total) and biliary excretion of digoxin, but affected little on beta-methyldigoxin clearances. These results suggest that P-gp-mediated drug interactions can easily occur in digoxin, but hardly in beta-methyldigoxin. These findings may give a clue in selecting these digitalis compounds in clinical use, towards escape from P-gp-mediated drug interactions or reduction of interindividual variations.

Role of KCNE1-dependent K+ fluxes in mouse proximal tubule.

The electrochemical gradient for K+ across the luminal membrane of the proximal tubule favors K+ fluxes to the lumen. Here it was demonstrated by immunohistochemistry that KCNE1 and KCNQ1, which form together the slowly activated component of the delayed rectifying K+ current in the heart, also colocalize in the luminal membrane of proximal tubule in mouse kidney. Micropuncture experiments revealed a reduced K+ concentration in late proximal and early distal tubular fluid as well as a reduced K+ delivery to these sites in KCNE1 knockout (-/-), compared with wild-type (+/+) mice. These observations would be consistent with KCNE1-dependent K+ fluxes to the lumen in proximal tubule. Electrophysiological studies in isolated perfused proximal tubules indicated that this K+ flux is essential to counteract membrane depolarization due to electrogenic Na+-coupled transport of glucose or amino acids. Clearance studies revealed an enhanced fractional urinary excretion of fluid, Na+, Cl-, and glucose in KCNE1 -/- compared with KCNE1 +/+ mice that may relate to an attenuated transport in proximal tubule and contribute to volume depletion in these mice, as indicated by higher hematocrit values.

A method to estimate urinary electrolyte excretion in patients at risk for developing cerebral salt wasting.

Two major criteria are necessary to diagnose cerebral salt wasting (CSW): a cerebral lesion and a large urinary excretion of Na+ and Cl- at a time when the extracellular fluid (ECF) volume is contracted. Nevertheless, it is difficult for the physician to confirm from bedside observation that a patient has a contracted ECF volume. Hyponatremia, although frequently present, should not be a criterion for a diagnosis of salt wasting. A contracted ECF volume is unlikely if there are positive balances of Na+ and Cl-. The goal of this study was to assess the accuracy of calculating balances for Na+ plus K+ and of Cl- over 1 to 10 days in an intensive care unit (ICU) setting. A prospective comparison of measured and estimated quantities of Na+ plus K+ and of Cl- excreted over 1 to 10 days in 10 children and 12 adults who had recently received a traumatic brain injury or undergone recent neurosurgery. Plasma concentrations of electrolytes were recorded at the beginning and end of the study period. The total volumes infused and excreted and the concentrations of Na+, K+, and Cl- in the infusate were obtained from each patient's ICU chart. The electrolytes in the patients' urine were measured and calculated. Correlations between measured and calculated values for excretions of Cl- and of Na+ plus K+ were excellent. Mass balances for Na+ plus K+ and for Cl- can be accurately estimated. These data provide information to support or refute a clinical diagnosis of CSW. The danger of relying on balances for these electrolytes measured within a single day to diagnose CSW is illustrated.

Plasma, urinary and fecal potassium changes in athletes during ambulatory, periodic, and continuous hypokinetic conditions

Objectives: Prolonged hypokinesia (HK) induces significant electrolyte changes, but little is known about the effect of prolonged periodic hypokinesia on plasma, urinary, and fecal K. The aim of this study was to measure potassium (K) changes during prolonged periodic (PHK) and continuous (CHK). Design and methods: Studies were done during the pre HK and HK periods. Thirty male athletes were chosen as subjects. They were divided equally into three groups: unrestricted ambulatory control subjects (UACS), continuously hypokinetic subjects (CHKS), and periodically hypokinetic subjects (PHKS). The CHKS group was kept on a running distance of 0.7 km/day, while the PHKS group kept on a running distance of 0.7 and 11.7 km/day for 5 days and 2 days per week, respectively. The UACS group was on a running distance of 11.7 km/day. Results: The following were measured: fecal K excretion; urinary K; sodium (Na) and chloride (Cl) excretion; plasma K; Na and Cl concentration; plasma renin activity (PRA) and plasma aldosterone (PA) concentration; physical characteristics; and peak oxygen uptake. Fecal K, urinary K, Na and Cl excretion, plasma K, Na and Cl concentration, and PRA and PA concentration, increased significantly (p ≤ 0.01) in the CHKS and PHKS groups when compared with the UACS group. Body weight and VO 2 peak decreased significantly ( p ≤ 0.01) in the CHKS group, while body weight increased and VO 2 peak decreased significantly ( p ≤ 0.01) in the PHKS group when compared with the UACS group. The measured parameters changed much more in the PHKS group than in the CHKS group. By contrast, the measured parameters did not change significantly in the UACS group when compared with the baseline control values. Conclusion: It was shown that prolonged PHK and CHK induce significant plasma and excretory K changes; however, plasma and excretory K changes were much greater in the PHKS group than in the CHKS group. It was concluded that the greater the stability of muscular activity, the smaller the plasma, urinary, and fecal K changes during prolonged HK.

Potassium supplements' effect on potassium balance in athletes during prolonged hypokinetic and ambulatory conditions.

Electrolyte supplements may be used to prevent changes in electrolyte balance during hypokinesia (diminished movement). The aim of this study was to measure the effect of potassium (K) supplements on K balance during prolonged hypokinesia (HK). Studies were done during 30 d of a pre-HK period and during 364 d of an HK period. Forty male athletes aged 25.1+/-4.4 yr were chosen as subjects. They were divided equally into four groups: unsupplemented ambulatory control subjects (UACS), unsupplemented hypokinetic subjects (UHKS), supplemented hypokinetic subjects (SHKS) and supplemented ambulatory control subjects (SACS). The SHKS and UHKS groups were kept under an average walking distance of 0.7 km/d. The SACS and SHKS groups were supplemented daily with 50.0 mg elemental potassium chloride (KCl) per kilogram body weight. The K balance, fecal K excretion, urinary K, sodium (Na), and chloride (Cl) excretion, plasma K, Na, and Cl concentration, plasma renin activity (PRA) and plasma aldosterone (PA) concentration, anthropometric characteristics and peak oxygen uptake were measured. Negative K balance, fecal K excretion, urinary K, Na, and Cl excretion, plasma K, Na, and Cl concentration, and PRA and PA concentration increased significantly (p < or = 0.01), whereas body weight and peak oxygen uptake decreased significantly in the SHKS and UHKS groups when compared with SACS and UACS groups. However, the measured parameters changed much faster and much more in SHKS group than UHKS group. By contrast, K balance, fecal, urinary, and plasma K, plasma hormones, body weight, and peak oxygen uptake did not change significantly in the SACS and UACS groups when compared with the baseline control values. It was concluded that prolonged HK induces a significant negative K balance associated with increased plasma K concentration and urinary and fecal K excretion. However, negative K balance appeared much faster and was much greater in the SHKS group than UHKS group. Thus, K supplementation was not effective in preventing negative K balance during prolonged HK.

Effects of Dietary Cation-Anion Difference on the Acid-Base Status of Dry Cows

Responses in dry matter intake (DMI) and acid-base balance to three sources of anionic salts (dietary cation-anion difference = –63 to –40 meq/kg of dry matter), an acidified fermentation by-product, MgSO4·7H2O + NH4Cl, and MgSO4·7H2O + CaCl2·2H2O + CaSO4, were evaluated relative to the responses of cows fed a control diet (dietary cationanion difference = 203 meq/kg of dry matter) that did not contain anionic salts. Diets were fed for 1-wk periods to eight nonlactating Holsteins assigned to two replicated 4 × 4 Latin squares. Daily DMI increased as time of access to the diet increased up to d 5; mean DMI over d 5 to 7 was reduced by dietary anionic salts. Diets containing anionic salts induced a mild metabolic acidosis that was completely compensated by nonrespiratory mechanisms (decreased blood bicarbonate and base excess; pCO2 and pH values were unaffected). Urinary pH values and bicarbonate excretion were reduced, and urinary NH4+ and titratable acidity excretion were increased, for cows fed diets containing anionic salts. Strong ion difference in urine was decreased by dietary anionic salts because of the relatively greater excretions of Cl− and S2− versus Na+ and K+ by cows fed these diets. Dietary anionic salts decreased mean ruminal pH by 0.12 units, possibly because of the reduced strong ion difference of ruminal fluid. Dietary anionic salts increased mean ruminal NH3 concentration by 2.2mM, probably because of the higher nonprotein N content of these diets. The strong negative relationship (r2 = 0.95) between urinary pH and net acid excretion by cows fed the diets containing anionic salts suggested that urinary pH measurement might be a useful tool to assess the degree of metabolic acidosis that was imposed by dietary anionic salts.

Determination of Urinary Oxalate with Cl− and NO−3 Insensitive Oxalate Oxidase Purified from Sorghum Leaf

Methods for determination of urinary oxalate, which use oxalate oxidase from mosses, barley, banana peel, and beet stems, may suffer interference from physiological concentrations of Cl− and NO−3, usually found in urine (1)(2)(3)(4)(5)(6). The usual daily excretion of Cl− and NO−3 are 10–15 g/day and 0.5 g/day, respectively. The potential interference of these anions is removed either by passing the urine through an ion-exchange column or by precipitation of oxalate from urine and its redissolution prior to oxalate assay (1)(7). This pretreatment complicates the procedure; consequently, the sensitivity and reproducibility of the determination often suffer. In our laboratory, we have purified an oxalate oxidase from leaves of 10-day-old seedling plants of grain sorghum (CSH-5), which is insensitive to physiological concentrations of Cl− and NO−3 (8). In the present report, we describe a new method of oxalate determination using grain sorghum leaf enzyme, which does not suffer from Cl− and NO−3 interference. The seeds of grain sorghum ( Sorghum vulgare var CSH-5) were a gift from M/s Nath Seeds Ltd. (Aurangabad, India). The 10-day-old seedling plants were raised from these seeds in the laboratory according to our method published previously (8). The leaves were collected and …

Minimum urine flow rate during water deprivation: Importance of the permeability of urea in the inner medulla

We evaluated whether altering the rate of excretion of sodium (Na) and chloride (Cl) when antidiuretic hormone (ADH) acts would cause urea to behave as an 'effective' or 'ineffective' urinary solute. Urine composition was compared to that in the excised papillary tip in rats treated with DDAVP while on a normal or a low electrolyte diet; half the rats were given a urea load. Studies were also carried out in humans who were water restricted for 12 to 16 hours and given DDAVP. One group had a high rate of NaCl excretion induced by a thiazide diuretic, while the other group consumed a low salt diet to decrease the rate of excretion of electrolytes. Urea (3 mmol/kg) was ingested after the control urine samples were collected. On the high salt protocols, the urine flow rate was directly proportional to the rate of excretion of electrolytes ('non-urea' osmoles) and there was no change in the 'non-urea' osmolality despite large changes in Na and Cl excretion rates. After urea was administered, there was no change in urine flow rate, 'non-urea' osmolality, or 'non-urea' osmole excretion rate, whereas the urinary urea concentration, urine osmolality and the rate of excretion of urea were higher. The papilla of the salt-loaded rats had a similar urea concentration to that in the urine. In contrast, in the low electrolyte excretion protocols, the sum of the concentrations of 'non-urea' osmoles in the urine was much lower than that in the excised papilla, and the converse applied to urea. Similar changes were observed in the composition of the urine in human subjects with high and low rates of excretion of electrolytes. We conclude that urea appears to be an 'ineffective' urine osmole when there is a high rate of salt excretion, whereas urea is an 'effective' osmole when there is a low rate of excretion of electrolytes.

Negative modulation of nitric oxide production by neurotensin as a putative mechanism of the diuretic action of SR 48692 in rats.

1. We investigated the effect of the non-peptide neurotensin (NT) antagonist SR 48692 on renal function in rats and the involvement of nitric oxide (NO) in the diuretic action of this compound. 2. In fed animals, SR 48692 dose-dependently (0.5 to 12.5 mg kg-1, p.o., 0.03 to 1 mg kg-1, i.p. and 0.1 to 1 microgram/rat, i.c.v.) increased urine output and urinary excretion of Na+, K+ and Cl- and reduced urine osmolality. The diuretic activity was also evident in water-deprived, fasted animals and in fasted, water-loaded rats. 3. NT (0.1 microgram/rat, i.c.v.) had no effect on urine output in fed rats, but reduced the diuretic action of SR 48692 (1 microgram/rat, i.c.v.). The opposite result was obtained in fasted, water-loaded animals: NT dose-dependently (0.01 and 0.1 microgram/rat, i.c.v.) inhibited diuresis and this effect was significantly inhibited by i.c.v. SR 48692. In this experimental condition, SR 48692 did not further increase the on-going diuresis. 4. The NO synthesis inhibitor N(1)-nitro-L-arginine methyl ester (L-NAME; 30 mg kg-1, i.p.) alone had no effect on urine output in fed rats but prevented the diuretic action of i.c.v. or i.p. SR 48692; L-arginine (1 g kg-1, i.p.) but not D-arginine (1 g kg-1, i.p.) restored the SR 48692-dependent increase in diuresis, L-NAME had no effect on furosemide-stimulated diuresis. 5. Systemically administered L-NAME or i.c.v. NT in fasted, water-loaded rats significantly reduced water diuresis but this effect was no longer seen in animals given i.p. L-arginine. Rats receiving i.c.v. NT, whose diuresis was significantly reduced, also excreted less nitrates and nitrites in urine. 6. Increased diuresis after central or systemic administration of SR 48692 to fed rats was paralleled by increased urinary excretion of nitrates and nitrites, this being consistent with peripheral enhancement of NO production after NT-receptor blockade by SR 48692. The increase in diuresis after furosemide also involved an increase of nitrates and nitrites in urine, but this effect was about half that attained with an equipotent diuretic dose of SR 48692. 7. In fed rats, the NO donor isosorbide-dinitrate, reduced systolic blood pressure (unlike SR 48692 which did not affect blood pressure) but also dose-dependently (1 and 5 mg kg-1, i.p.) stimulated urine output. 8. The overall effects of SR 48692 strongly support a link between the actions of endogenous NT, AVP and peripheral NO production in the modulation of renal excretion of water, Na+, K+ and Cl-.

Abnormal Reabsorption of Na&lt;sup&gt;+&lt;/sup&gt;/CI&lt;sup&gt;-&lt;/sup&gt; by the Thiazide-lnhibitable Transporter of the Distal Convoluted Tubule in Gitelman&amp;rsquo;s Syndrome

Eleven patients with Gitelman's syndrome and 23 controls underwent acute administration of the thiazide diuretic hydrochlorothiazide and/or the loop diuretic furosemide (FUR) in order to indirectly evaluate the activity of the two electroneutral Na+/Cl(-)-reabsorptive systems of the distal nephron, namely the thiazide-sensitive Na+-Cl- symporter of the distal convoluted tubule and the FUR-sensitive Na+-K+-2Cl- symporter of the loop of Henle. The patients were characterized by hypokalemia, mild metabolic alkalosis, hypomagnesemia, hypocalciuria, and reduced free water generation during maximally diluted diuresis which indicated reduced distal nephron NaCl reabsorption. The plasma Na and Cl levels were similar in patients and controls. Hydrochlorothiazide induced a significantly lower increase of urinary Na and Cl excretions in 6 patients with Gitelman's syndrome than in 6 controls, indicating reduced NaCl reabsorption by the thiazide-sensitive Na+/Cl- symporter of the distal convoluted tubule in Gitelman's syndrome. FUR induced a slightly higher increase of urinary Na and Cl excretions in 11 patients with Gitelman's syndrome than in 17 controls, in keeping with reduced NaCl reabsorption in tubular sites past the loop of Henle during FUR effect or increased NaCl reabsorption in the loop itself (as a compensatory mechanism for NaCl-reabsorptive defect in the distal convoluted tubule) or both. Our results confirm that the functional activity of the renal thiazide-sensitive Na+-Cl- cotransporter (but not of the FUR-sensitive carrier) is deficient in patients with Gitelman's syndrome, in keeping with the recently described genetic link between the syndrome and a wide variety of nonconservative mutations of the gene encoding the protein; it is suggested that dynamic studies with diuretic administration may be of diagnostic help in this condition.

Significance of residual renal functions of patients with end-stage renal failure undergoing continuous ambulatory peritoneal dialysis

It is generally accepted that residual renal function remains well-preserved longer with CAPD than with hemodialysis. However, consideration and impact of the contributory effects of residual renal function on the adequacy of renal replacement therapy has not been well defined. In this report, creatinine clearance (Ccr), Kt/V, normalized protein catabolic rate (nPCR) and urinary excretion of uremic solutes were studied in 26 stable CAPD patients with a four-bag exchange. Weekly Ccr, weekly Kt/V and nPCR were 62.3 +/- 20.2 l/week/1.73 m2, 1.77 +/- 0.35, and 0.90 +/- 0.13 g/kg/day, respectively. These parameters correlated significantly with the daily urine volume. The weekly Ccr and Kt/V of anuric patients seemed to be inadequate. Urinary excretion of urea nitrogen, Cr, Na, Cl, Pi and beta 2-microglobulin (beta 2-MG) were dependent upon the daily urine volume. Significant phosphorus and beta 2-MG excretion seemed to have an effect on the prevention of bone and joint complications, because serum iPTH and beta 2-MG levels increased after the patients fell into an anuric state. It was suggested from this study that CAPD should be started before the patient loses residual renal function because four bag exchange as the standard CAPD prescription might not be adequate once the patient loses urine excretion.

Influence of glucagon on GFR and on urea and electrolyte excretion: direct and indirect effects

Clearance experiments were performed in anesthetized male Wistar rats to determine the level of peripheral glucagon concentration required to elicit changes in glomerular filtration rate (GFR) and in solute excretion. Glucagon was intravenously infused at a rate of 1.25 (group G-1, n = 8), 3.75 (group G-3, n = 7), or 12.5 (group G-10, n = 7) ng.min-1.100 g body wt-1 for 100 min. Measurements were performed before, during, and after this infusion. Group G-10 resulted in a plasma concentration of glucagon severalfold higher than usually observed in peripheral blood after a protein meal but normal for the hepatic circulation. Group G-10 simultaneously increased GFR, plasma adenosine 3',5'-cyclic monophosphate (cAMP) concentration, and the excretion of water (i.e., urinary flow rate), Na, Cl, PO4, K, and urea. Some of the effects of glucagon on electrolyte excretion were also observed with group G-1 and/or G-3 and were fully reversible, suggesting a direct renal action of glucagon. The significant and reversible increase in K excretion in group G-3 suggests that glucagon exerts a direct stimulatory influence on K secretion in the distal nephron. Increases in urinary flow rate, PO4, Na, and urea fractional excretions were seen with group G-10 only and were not reversible, suggesting an indirect action of glucagon on the proximal tubule. Because glucagon stimulates cAMP formation in hepatocytes and because this cAMP is released in the blood and secreted by proximal tubule cells, cAMP of hepatic origin could induce a parathyroid hormone-like effect in this nephron segment. In summary, these experiments suggest that glucagon influences different aspects of renal function by a combination of direct and indirect (probably liver-dependent) effects.

Effects of NaCI supplementation before exercise on metabolism of water and electrolytes

SummaryFour horses were exercised for 2 h on a treadmill at up to 200 m/min 4 h after feeding. The trial included 3 treatments, control (A) and electrolyte supplementation provided either in the diet at the morning feeding (B) or 1 h before start of exercise (C). The horses were fed 2 meals/day of hay and concentrate (6.5 g dry matter, 13.8 mg Na, 66.6 mg K and 54.2 mg Cl/kg bwt per meal). The supplement was a mixture of grass meal (47.6%), sugar beet syrup (33.3%) and NaCl (19.1%); additional intake: Na 79.7, K 15.5 and Cl 165.6 mg/kg bwt. Hourly urine and blood samples were taken.Water intake and renal water excretion were significantly influenced by supplementary feeding (intake: A 35.5, B 49.9, C 55.6 ml/kg bwt/12 h; excretion: A 9.47, B 15.34, C 7.92 ml/kg bwt/12 h). The urinary Na and Cl excretion was significantly higher in treatment B (Na 24, Cl 55 mg/kg bwt/12 h) and C (Na 12, Cl 44 mg/kg bwt/12 h) as compared to A (Na 5, Cl 16.5 mg/kg bwt/12 h). Renal K output was less influenced by the different treatments, A 43, B and C 61 mg/kg bwt/12 h. However, the renal Na and Cl excretion was lower in relation to intake when horses received the supplement. In these cases, losses of water, Na and Cl via sweat were compensated for at the end of exercise and a positive balance therefore maintained 12 h after feeding. The total plasma protein concentration increased during exercise, indicating a reduction in plasma volume. The Na and K concentrations in plasma during exercise showed minor changes whereas the Cl concentrations decreased significantly by 2.6 (A), 4.0 (B) and 1.4 (C) mmol/l. Changes in plasma Na and Cl in treatments B and C occurred at constant higher levels than in treatment A.The results suggest a positive impact of NaCl suplementation on water and electrolyte metabolism in exercised horses. The increased water intake indicates that supplementary salt intake is more effective about 4 h than 1 h before exercise.

Dietary NaCl-restriction prevents the calciuria of KCl-deprivation and blunts the calciuria of KHCO3-deprivation in healthy adults

Previous studies have demonstrated that dietary potassium deprivation in healthy human subjects eating diets otherwise containing normal quantities of NaCl is accompanied by an increase in urinary calcium excretion. This increase in urinary Ca excretion occurs in association with reductions in urinary Na and Cl excretion together with trends for weight gain and is delayed for several days after the initiation of K-deprivation, suggesting that it is mediated by NaCl retention and expansion of the extra-cellular volume. The present studies were thus undertaken to determine whether dietary NaCl restriction prevents the calciuric effect of subsequent K-deprivation. When dietary NaCl intake was limited to 5 +/- 3 mmol/day among 10 healthy adults, subsequent deprivation of KCl (-67 mmol/day) in 5 subjects of deprivation of KHCO3 (-64 mmol/day) in 5 subjects prevented any significant increase in daily urinary Ca excretion during five days of K-deprivation. There was, however, a small but significant cumulative increase above control in urinary Ca excretion at the end of KHCO3-deprivation, averaging + 1.9 +/- 0.6 mmol; P < 0.05. When KCl was restored to the diets urinary Ca excretion increased while restoration of KHCO3 to the diets caused urinary Ca to fall to rates below control. We conclude that the calciuria of K-deprivation when NaCl is present in the diet is largely dependent upon NaCl retention by the kidneys and subsequent ECF-volume expansion. In addition, HCO3 is anti-calciuric.

Ontogenic changes in renal response to alpha 1-adrenoceptor stimulation in sheep.

The present study was designed to examine the effect of direct intrarenal infusion of the alpha 1-adrenoceptor agonist, phenylephrine, on urinary flow rate (UFR) and on renal Na and Cl excretion in conscious and chronically instrumented fetal (128-133 days gestation, term 145 days), newborn (6-12 days), and adult sheep. Five different renal concentrations of phenylephrine, varying from 5 +/- 1 to 72 +/- 2 ng/ml, were studied. Low renal phenylephrine concentration (< or = 12 +/- 1 ng/ml) induced a significant renal vasoconstrictor response in fetuses but not in newborn and adult sheep. The effects of intrarenal phenylephrine infusion on UFR and fractional excretion of Na (FENa) was greater (P < 0.05) in newborn lambs than in fetal and adult sheep. At a renal concentration of phenylephrine between 9 +/- 1 and 12 +/- 1 ng/ml, the percent decrease in UFR was greater (P < 0.05) in newborn lambs (-19.1 +/- 4.7%) than in fetal (9.8 +/- 8.9%) and adult sheep (-3.3 +/- 3.9). The percent decrease in FENa at renal concentration of phenylephrine between 18 +/- 1 and 24 +/- 1 ng/ml was also significantly (P < 0.05) larger in newborn lambs (-20.2 +/- 2.8%) than in fetal (-8.0 +/- 3.1%) and adult sheep (-11.2 +/- 2.6%). In summary, the present results indicate that the fetal kidney has a limited ability to increase sodium reabsorption in response to stimulation of alpha-adrenoceptors and that the effect of renal alpha-adrenoceptor stimulation on urinary volume and urinary sodium excretion increases during the newborn period.