Renal sodium excretion after oral or intravenous sodium loading in sodium-deprived normotensive and spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats that had been on a low sodium diet for 3 days were given 1.5 mmol sodium chloride kg-1 body weight either orally or intravenously. The rats receiving an oral sodium load showed a greater natriuresis than those receiving the same saline load intravenously. No increase of renal sodium excretion was observed when the rats received a hypertonic mannitol solution orally. The cumulative sodium excretion during the 8 h following oral loading was two to three times larger in SHR than in WKY, whereas no difference between strains could be demonstrated after giving saline intravenously. Furthermore, after switching from normal to low sodium diet the rate of decrease of renal sodium excretion was greater in SHR than in WKY rats. It is proposed that there exists a gastrointestinal sensory mechanism for sodium controlling the renal sodium excretion. Furthermore, it is suggested that the function of this mechanism differs between SHR and WKY.     

Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients

The relationship between blood pressure and sodium (Na) excretion is less steep in hypertension caused by increased renal tubular reabsorption. We recently demonstrated that one mutation in rat alpha-adducin gene: (1) is responsible for approximately 50% of the hypertension of MHS rats, and (2) stimulates tubular Na-K pump activity when transfected in renal epithelial cell, suggesting that its pressor effect may occur because an increased tubular reabsorption. Linkage and association studies demonstrated that the alpha-adducin locus is relevant for human hypertension. A point mutation (G460W) was found in human alpha-adducin gene, the 460W variant (G/W) is more frequent in hypertensives than in normotensives. The aim of this study was to test whether acute changes in body Na may differently affect blood pressure in humans as a function of alpha-adducin genotype. The pressure-natriuresis relationship was analyzed in 108 hypertensive using two different acute maneuvers: Na removal (furosemide 25 mg p.o.) and, two days later, Na load (310 mmoles i.v. in 2 hr). We found that 80 patients were wild-type homozygous (G/G), 26 were G/W heterozygous, and 2 were W/W homozygous with similar blood pressure, age body mass index, gender, plasma and urinary sodium and potassium. In basal condition G/W-W/W patients showed a lower plasma renin activity and fractional excretion of Na. In either case the pressure-natriuresis relationship was less sleep in G/W-W/W than in G/G patients, obviously negative for Na depletion with furosemide (-0.011 +/- 0.004 vs. -0.002 +/- 0.002 mm Hg/mumol/min, P < 0.03), and positive for Na load (0.086 +/- 0.02 vs. 0.027 +/- 0.007 mm Hg/mumol/min, P < 0.001). The finding of reduced slope after Na depletion or Na load supports the hypothesis that, as MHS rats, humans bearing one W alpha-adducin variant display an increased of renal tubular sodium reabsorption.     

Urinary dopamine and sodium excretion in spontaneously hypertensive rats

We measured urinary dopamine in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before (days 0-6) and during high-salt diet, in the absence (days 6-10) and presence (days 10-14) of added L-dopa (2 mg/kg/day by gavage). Urinary excretion of sodium (UNaV) increased 20-fold during intake of chow containing 8% NaCl in both strains. Systolic blood pressure (SBP) of SHR increased slightly (9 +/- 4 mmHg; p < 0.05) on the high-salt diet, whereas SBP did not change in WKY. Urinary dopamine excretion was not different between strains in the basal state, and was as great or greater in SHR than WKY during high-salt intake with and without added L-dopa. SBP was unaffected by L-dopa administration and UNaV did not increase or differ between strains despite higher urinary dopamine excretion in SHR. We conclude that renal dopamine formation in vivo is not diminished in SHR, compared with WKY, on normal or high-salt diets, and that elevation of renal dopamine formation secondary to L-dopa administration is not associated with reductions in SBP or altered UNaV in these rats.     

Reduced mercury excretion with feces in germfree mice after oral administration of methyl mercury chloride

When methyl mercury chloride was administered orally the amount of mercury excretion with feces of germfree mice was noticeably lower than that of the control mice. Germfree mice excreted 24 percent of the administered mercury within 10 days of administration while the control mice excreted 46 percent. Mercury retention in the organs of germfree mice was slightly higher than in the control mice. These results suggest that the existence of microorganisms in animal intestines are concerned with mercury excretion in the animal body.     

Oxygen administration increases plasma digoxin-like substance and renal sodium excretion in chronic hypoxic patients

Despite the absence of cardiac or renal pathologies, edema and mild hyponatremia may often occur in patients affected by chronic obstructive pulmonary disease (COPD). Therefore, it has been suggested that hypoxia may influence the release of different hormones regulating renal sodium handling. To evaluate the effect of hyperoxia and O2 removal on plasma digitalis-like substance (DLS) levels, 9 patients affected by COPD and 7 normal subjects were studied. After 1 h in supine position, O2 was administered for 3 h by a tight-fitting face-mask. Blood samples for plasma DLS were taken at time 0, 60, 180 min and then for 3 h after O2 removal. In normal subjects, plasma DLS did not vary after O2 administration (from basal values of 162.25 +/- 8.59 to 107.75 +/- 6.65 pg/ml at 180 min; NS), and O2 removal (143.7 +/- 16.87 pg/ml after 3 h from O2 removal; NS). On the contrary, in patients affected by COPD, plasma DLS levels increased during O2 administration (from basal values of 138.98 +/- 8.31 to 202.14 +/- 8.21 pg/ml at 180 min; p < 0.05), and returned to baseline levels (142.59 +/- 8.28 pg/ml) 3 h after O2 removal. In the same patients, DLS increase was accompanied by a rise in Na+ excretion (from 0.08 +/- 0.01 at time 0 to 0.16 +/- 0.02 mEq/min after 3 h of O2 administration; p < 0.05). In conclusion, our findings showed an oxygen-related increase in plasma DLS levels and in urinary Na+ excretion in patients affected by COPD. This phenomenon could promote Na+ urinary loss during prolonged O2 therapy in these patients and should be taken into account in their management.     

Sex hormone responses in healthy men and male patients with chronic obstructive pulmonary disease during an oral glucose load

The responses of serum testosterone, sex hormone-binding globulin (SHBG) and luteinizing hormone (LH) to an oral glucose tolerance test (OGTT) were investigated in 16 healthy subjects as well as in 11 normoxaemic and 10 hypoxaemic chronic obstructive pulmonary disease (COPD) patients. The latter group were investigated on two occasions, with and without oxygen therapy. Testosterone and apparent free testosterone concentration (AFTC) fell significantly in the healthy subjects as well as in the hypoxaemic patients on oxygen therapy (p < 0.01), whereas LH increased in all groups during the OGTT (p < 0.05). There were significantly higher SHBG levels (p < 0.01), and lower AFTC levels (p < 0.05) in the hypoxaemic group compared to the healthy subjects. In the hypoxaemic group short-term oxygen therapy increased basal AFTC significantly (p < 0.05). With oxygen therapy, the 120-min glucose levels fell significantly from 9.1 +/- 3.2 to 7.6 +/- 2.7 mmol l-1 (mean +/- SD) in the hypoxaemic group (p < 0.05). In conclusion, we have found the serum testosterone and AFTC levels to decrease after an oral glucose load in healthy subjects, together with a compensatory increase in LH. The same pattern is seen in COPD patients. The hypoxaemic patients have a reduced AFTC which is partly reversed by oxygen therapy.     

Chronic immobilization stress reduces sodium intake and renal excretion in rats

The influence of chronic exposure to immobilization (IMO) on sodium appetite as well as sodium and potassium renal excretion in adult male Wistar rats was studied. The animals were individually housed and all variables under observation were measured in metabolic cages the first, seventh, and thirteenth days once the experiment had started. Half of the rats had access to water, and the remainder of the rats had access to both water and saline solution (1.5% NaCl). IMO reduced the intake of saline solution. Renal water, sodium, and potassium excretion in those IMO rats having access to saline were lower than in control rats. The effects of IMO were very similar during all observation days; therefore no evidence of adaptation to repeated stress was found. The present data indicate the following: (i) IMO stress reduced sodium appetite, probably as a secondary effect to the deficit in sodium renal excretion; (ii) IMO caused antidiuresis and antikaliuresis, only in those rats taking saline solution; (iii) no adaptation to repeated IMO stress was found in any of the tested variables. The reduction of sodium appetite observed in stressed rats might be a homeostatic mechanism to maintain sodium balance after impairment of renal sodium excretion caused by stress.     

Renal excretion of sodium in individuals with stabilized renal graft function

In subjects with a transplanted kidney frequently tubular functions are impaired even when the glomerular filtration is within the normal range. In the present work the authors are dealing in more detail with the problem of tubular sodium reabsorption in the transplanted kidney. The purpose of the investigation was to assess to what extent these changes can be explained as the consequence of adaptational changes due to reduction of the number of nephrons and whether these changes have to be taken into consideration in the differential diagnosis of acute changes of graft function. The glomerular filtration rate (GF) was assessed on the basis of polyfructosan clearance, fractional sodium and potassium excretion (FENa and FEK) in a group of 12 subjects with a stabilized function of a transplanted kidney (group A), in 11 subjects after nephrectomy in healthy donors for transplantation (group B) and in 27 subjects after nephrectomy indicated for a pathological process in one kidney (group C). The mean values of GFR were as follows: Group A: 1.21 (+/- 0.19)ml/s/1.73 sq.m Group B: 1.19 (+/- 0.17)ml/s/1.73 sq.m Group C: 1.24 (+/- 0.21)ml/s/1.73 sq.m The mean values of GFR in different groups did not differ significantly. The mean values of FENa in different groups were as follows: Group A: 3.02 (+/- 1.59)% Group B: 2.05 (+/- 0.77)% Group C: 2.01 (+/- 1.17)% The mean value of FENa in group A was significantly higher than the mean value in group B (p < 0.01) and in group C (p < 0.01). The assembled findings support the idea that reduced tubular sodium reabsorption in the transplanted kidney (with a stabilized value of GFR) cannot be explained only as a manifestation of adaptation of tubular function as a result of the reduced number of functioning nephrons. The persisting osmotic sodium diuresis in the transplanted kidney must be viewed from the aspect of possibly impaired water preservation and the development of dehydration associated with a drop of GFR and must be differentiated from rejection.     

Bone mineral recovery after parathyroidectomy in patients with primary and renal hyperparathyroidism

Patients with hyperparathyroidism (HPT) generally display reduced bone mass due to excessive PTH activity. The effect of parathyroidectomy on bone mass changes in different types of HPT, however, is not well understood. Bone mineral density (BMD) was measured in the distal radius, total body, femoral neck, and lumbar spine by dual energy x-ray absorptiometry in four groups of patients with different hyperparathyroid conditions: primary symptomatic HPT (n = 54), primary asymptomatic (mild) HPT (n = 24), HPT associated with hemodialysis (n = 20), and HPT associated with renal transplant (n = 30). Subsets of patients with primary symptomatic HPT (n = 52), HPT associated with hemodialysis (n = 19), and HPT associated with renal transplant (n = 15) underwent parathyroidectomy, and bone density was measured longitudinally for 3 yr. Patients with primary asymptomatic (mild) HPT did not undergo surgery and were followed prospectively. Before surgery, all groups showed a greater reduction of bone mineral density in cortical bone (distal radius) than in predominantly trabecular bone (lumbar spine). In primary symptomatic HPT, the BMD z-score of the distal radius was -1.80 +/- 0.21 (+/-SEM), and the corresponding figures for the total body, femoral neck, and lumbar spine were -0.60 +/- 0.15, -0.54 +/- 0.14, and -0.53 +/- 0.18 compared with those of an age- and sex-matched reference group. In renal HPT BMD z-scores were -2.51 +/- 0.38 (hemodialysis patients) and -2.83 +/- 0.43 (renal transplant patients) for the distal radius and between -0.81 and -1.46 for the other measured sites. After parathyroidectomy, BMD increased by 1-8% at all sites in patients with primary symptomatic HPT and HPT associated with renal transplant. The largest increase in bone mass was observed in patients with HPT associated with hemodialysis, in whom the improvement amounted to 7-23%. In patients with primary HPT and HPT associated with hemodialysis, this increase in bone density resulted in virtual recovery from their preoperative bone loss. The majority of patients with asymptomatic primary HPT disease (n = 21) maintained their bone density during the follow-up period and have not shown evidence of increases in serum calcium or PTH levels, but three patients followed conservatively underwent parathyroidectomy due to progressive deterioration of BMD. We conclude that, regardless of the etiology, a large proportion of HPT patients show reduced bone density. In patients with primary symptomatic HPT and patients with HPT associated with hemodialysis, bone density increases after parathyroidectomy to an extent that largely restores the preoperative bone loss. However, no anabolic effect of parathyroidectomy on bone mass was observed in patients with HPT associated with renal transplant, probably because of their immunosuppressive therapy.     

An oral glutamine load enhances renal acid secretion and function

In a recent study, a small oral glutamine load acutely elevated plasma bicarbonate concentrations in healthy adults (Am J Nutr 1995;61:1058-61). The present study was designed to elucidate the renal mechanism underlying the base-generating response to L-glutamine. Accordingly, vehicle (489 mL diet soda) or vehicle plus 2 g L-glutamine (28 mg/kg body wt) was ingested and the gain in extracellular fluid volume bicarbonate was compared with renal acid elimination as either ammonium excretion or tubular acid secretion (titratable acid plus bicarbonate reabsorption). Vehicle alone, which contained 27 mmol acid, did not increase extracellular fluid volume bicarbonate over the 90-min period. In contrast, L-glutamine increased plasma bicarbonate concentration (from 25.4+/-2 to 27.9+/-1 mmol/L, P < 0.05) and extracellular fluid volume bicarbonate by an estimated 39+/-10 mmol. When added to that required to neutralize the ingested acid, the combined total for new bicarbonate generated gave an estimated 66+/-10 mmol. Surprisingly, ammonium excretion accounted for < 2% of this newly generated bicarbonate. However, acid secreted and excreted as net acid (5.2+/-4.0 mmol/90 min) as well as that coupled to enhanced bicarbonate reabsorption (76+/-20 mmol/90 min) readily accounted for the estimated base gain (81+/-24 compared with 66+/-10 mmol/90 min). Concomitant with enhanced renal acid secretion, the oral glutamine load elicited an increase in glomerular filtration rate. These results rule out a role for L-glutamine as a direct precursor of bicarbonate and instead point to an indirect role in accelerating acid secretion, apparently coupled to increased glomerular filtration rate.     

Pregnant women with impaired tolerance to an oral glucose load in the afternoon: evidence suggesting that they behave metabolically as patients with gestational diabetes

OBJECTIVE: In previous studies we observed the existence of a circadian variation of the blood glucose response to oral glucose in pregnant women with higher values at 4 PM. Some women with increased risk of diabetes with normal oral glucose tolerance tests at 8 AM also had values above maximum normal levels at 4 PM. The aim of this trial was to determine the clinical significance of this impaired tolerance in the afternoon. STUDY DESIGN: Seventy-seven pregnant women with normal risk of diabetes (65 of normal weight and 12 overweight), 75 with increased risk of diabetes (26 overweight), and 12 patients with gestational diabetes were incorporated in the study. All women underwent two oral glucose tolerance tests (1.5 gm/kg) at 31 to 32 weeks' gestation at 8 AM and 4 PM with a 1-week interval. At 33 weeks' gestation a whole-day blood glucose profile was performed with usual food intake; samples were withdrawn before each meal and at 30, 60, and 120 minutes after each meal. The weight of the newborns was recorded. RESULTS: (1) Results of oral glucose tolerance tests confirmed a circadian variation of the response in all groups; (2) 37 women with increased risk of diabetes had higher values after oral glucose tolerance testing than the normal threshold at 4 PM but not at 8 AM; (3) among women with normal risk of diabetes all values were within the normal range despite the circadian variation; (4) blood glucose levels during whole-day profiles were normal in women with normal risk of diabetes and with increased risk of diabetes with normal oral glucose tolerance testing at 4 PM, whereas all women with increased risk of diabetes and impaired tolerance in the afternoon showed hyperglycemic episodes; (5) the percentage of newborns with high weight (>90th percentile) among women with increased risk of diabetes and abnormal oral glucose tolerance tests at 4 PM was similar to the percentage found in women with gestational diabetes and much higher than the one observed in women with normal oral glucose tolerance tests in the afternoon. CONCLUSIONS: The impairment of the response to oral glucose tolerance testing seen in some patients with increased risk of diabetes at 4 PM but not at 8 AM seems of clinical significance in view of the abnormal whole-day blood glucose profile these women had and the weights of the newborns.     

Nonoliguric acute renal failure associated with a low fractional excretion of sodium

Measurement of the fractional excretion of sodium has been recommended as a useful clinical tool in evaluating acute renal failure. Six patients with nonoliguric acute renal failure had a fractional excretion of sodium less than or equal to 1.0%; these patients had severe liver dysfunction, which suggested a sodium-avid state. A review of the literature showed that in patients with other sodium-avid states (congestive heart failure, nephrotic syndrome, and burns) the fractional excretion of sodium was frequently less than or equal to 1.0%. The fractional excretion of sodium is thus a less useful diagnostic test in patients whose clinical state makes them sodium avid.     

Potassium and sodium intake and excretion in calcium stone forming patients

We reviewed the results of 15 patients (16 feet) in whom a hallux valgus procedure had failed. Salvage was by proximal crescentic first metatarsal osteotomy with distal soft-tissue reconstruction. Results based on a clinical scale considering the level of pain, activity limitations, support requirement, footwear limitations, and alignment were good in 11, fair in two, and poor in three. Patients were satisfied with the results in 10 feet, satisfied with reservations in four feet, and dissatisfied in two feet. Complications were: transfer metatarsalgia in three, hallux varus in one, and osteotomy nonunion in one. One of the patients required reoperation to bone graft a proximal osteotomy. Metatarsal osteotomy was helpful in the salvage treatment of recurrent, symptomatic hallux valgus when the first metatarsophalangeal joint was functional and painless.     

Urinary norepinephrine excretion in elderly hypertensive patients during administration of fusaric acid

The urinary norepinephrine excretion during fusaric acid calcium salt administration was examined in 5 elderly hypertensive patients by double blind cross-over method. The average daily excretion of the last 5 days during fusaric acid calcium salt or placebo administration of 5 weeks' duration was compared in each patient. In 4 patients except for one, the average daily urinary excretion of norephinephrine during fusaric acid calcium salt administration showed an increase, being highly significant (p less than 0.01) statistically, when compared with that during placebo administration, the latter being essentially unchanged. In the one patient, however, the average daily urinary excretion of norepinephrine was significantly higher during placebo administration than that during fusaric acid calcium salt administration. The relationship between the changes in the average daily urinary excretion of norepinephrine and those in blood pressures seemed to be not consistent. The mechanism which brought about an increased norepinephrine excretion in the urine of the hypertensive patients is not obscure at present.     

A labile sodium pump inhibitor from the peritoneal dialysate of hypertensive renal failure patients: estimates of potency

Estimations of concentration of the labile sodium pump inhibitor isolated from human peritoneal dialysate were made using supercritical fluid chromatography coupled to flame ionization detection to determine the quantity of this factor in half of a purified preparation of the factor compared to the bioactivity of the other half in different assays. Ouabain was used for comparison. The labile factor appeared to be 30 times more effective than ouabain against canine renal [Na,K]ATPase. Moreover, this same factor appeared to be approximately 1,000 times more potent than ouabain in causing vascular smooth muscle contraction. The differences between this labile sodium pump inhibitor and ouabain most likely reflect their respective binding affinities. The assay differences in half maximal response to the labile sodium pump inhibitor may be due to differences in sodium pump alpha isoform sensitivity.     

The role of brain cholinergic system in renal sodium, potassium and water excretion in rats

In anesthetized rats intracerebroventricular (i. c. v.) injection of cholinergic agonist carbachol induced significant natriuresis, kaliuresis and diuresis (P < 0.05). Among them, the degree of natriuresis was changed with carbachol in a dose-dependent manner (r = 0.9997, P < 0.05). These responses were completely blocked by cholinergic M receptor antagonist atropine or N receptor antagonist hexamethonium pretreatment. Such effects of carbachol were inhibited in part by pretreatment with adrenergic alpha receptor antagonist phentolamine. These results indicate that the natriuresis, kaliuresis and diuresis induced by i. c. v. injection of carbachol were primarily mediated by both muscarinic and nicotinic receptors in the brain, while the effect was in part mediated secondarily via adrenergic alpha receptor.