Biomedical subjects

M M Popovtzer

Publications and source records attributed to M M Popovtzer.

At least 19 recordsLinked to original sources

PubMed1992

Assessment of combined 24,25(OH)2D3 and 1 alpha (OH)D3 therapy for bone disease in dialysis patients.

An increasing body of experimental data suggests a role for 24,25(OH)2D3 in bone metabolism. The present study was carried out to assess a possible therapeutic role of this vitamin D metabolite in renal osteodystrophy. Twenty-two chronic dialysis patients, most of whom were previously maintained on 1 alpha (OH)D3 therapy, received additional treatment with 10 micrograms/day 24,25(OH)2D3 and were compared to 19 patients receiving 1 alpha (OH)D3 alone. Analysis of transiliac bone biopsies obtained at study entry and following 10-16 months of treatment revealed that the combined therapy produced a decrease in bone turnover. Specifically, the addition of 24,25(OH)2D3 inhibited an increase in trabecular bone volume (BV/TV) and suppressed osteoclastic parameters. Thus BV/TV increased from 26.2 +/- 8.6 to 32.1 +/- 7.5% (p < 0.01) in the 1 alpha (OH)D3 group, but it remained unchanged in the combined therapy group. In contrast, the eroded surface (ES/BS), the osteoclast surface (Oc.S/BS), and the osteoclast numbers were significantly suppressed in patients receiving both 24,25(OH)2D3 and 1 alpha (OH)D3, as compared with those receiving 1 alpha (OH)D3 alone (p < 0.01, p < 0.01, and p < 0.001, respectively). These improvements were independent of changes in 1 alpha (OH)D3 dosage. The extent of bone aluminium deposits was unrelated to the administration of 24,25(OH)2D3 or to its effect. 24,25(OH)2D3 therapy was not associated with any adverse effects.

24,25-Dihydroxyvitamin D 3↗

PubMed1992

Hyperlipidemia associated with alpha-mercaptopropionylglycine therapy for cystinuria.

Treatment of cystinuria with alpha-mercaptopropionylglycine has been associated with fewer side effects than traditional therapy with D-penicillamine. In this report, we describe a patient who developed hyperlipidemia secondary to alpha-mercaptoproprionylglycine therapy. This abnormality resolved after the therapy was discontinued and did not recur with lower dose therapy. Patients treated with alpha-mercaptoproprionylglycine should be monitored closely for the development of lipid abnormalities.

Adult↗

PubMed1992

Indomethacin and sodium retention in the rat: role of inhibition of prostaglandin E2 synthesis.

1. To further explore the Na(+)-retaining effect of indomethacin along the whole length of the nephron, the Na(+)-K(+)-ATPase activity of isolated tubules from indomethacin-pretreated rats was compared with that of tubules isolated from intact rats and exposed directly to prostaglandin E2. 2. Indomethacin increased Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (+24%, P < 0.001 versus control), proximal straight tubule (+75%, P < 0.001 versus control), medullary thick ascending limb (+68%, P < 0.001 versus control), cortical thick ascending limb (+7%, not significant) and cortical collecting duct (+18%, P < 0.025 versus control). In contrast, in the distal convoluted tubule indomethacin decreased Na(+)-K(+)-ATPase activity by -42% (P < 0.001 versus control). 3. Indomethacin also strongly increased Na(+)-K(+)-ATPase activity in the cortical collecting duct of adrenalectomized rats. 4. In isolated tubules from control rats, prostaglandin E2 reduced Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (-33%, P < 0.05), proximal straight tubule (-60%, P < 0.001), medullary thick ascending limb (-43%, P < 0.001), cortical thick ascending limb (-25%, P < 0.001) and cortical collecting duct (-45%, P < 0.001) and in the distal convoluted tubule, prostaglandin E2 increased Na(+)-K(+)-ATPase activity (+32%, P < 0.05). 5. That these changes in Na(+)-K(+)-ATPase activity in indomethacin-pretreated rats and prostaglandin E2-treated controls are similar in magnitude but occur in opposite directions suggests that the response to indomethacin is mediated by inhibition of prostaglandin E2 synthesis in the nephron. In the cortical collecting duct the effect of indomethacin is aldosterone-independent.

Adrenalectomy↗

PubMed1992

Thiazide therapy for ACTH-induced hypercalciuria and nephrolithiasis.

A one-year-old boy presented with hypercalciuria and nephrolithiasis following a course of ACTH therapy for infantile spasms. After a successful cystolithotripsy, therapy with chlorothiazide was followed by regression of the hypercalciuria within 42 months. Neither nephrolithiasis nor nephrocalcinosis recurred. Therapy with thiazides to prevent hypercalciuria caused by ACTH is proposed.

Adrenocorticotropic Hormone↗

PubMed1992

Angiotensin-converting enzyme inhibitors and glycosuria.

Renal glycosuria associated with the use of angiotensin-converting enzyme inhibitors has been previously reported in two patients. A third patient was studied who developed isolated glycosuria associated with lisinopril therapy. As in the two previously described patients, this patient had a normal serum glucose level, underlying hypertension, and onset of glycosuria between 2 and 16 weeks after initiation of therapy with an angiotensin-converting enzyme inhibitor. The patient had renal artery stenosis with elevated renin levels. Age, time until resolution of glycosuria, and a rise in serum creatinine level did not have a consistent relationship with glycosuria associated with angiotensin-converting enzyme inhibitor therapy. Since glycosuria was the only defect noted, without evidence of any other urinary solutes, angiotensin-converting enzyme inhibitors may exert an effect on the glucose-specific proximal tubule transport system.

Adult↗

PubMed1991

24,25(OH)2D3 affects the calcemic effects of 1,25(OH)2D3 by mechanisms independent of intestinal calcium absorption.

To better define the interaction between 1,25(OH)2D3 and 24,25(OH)2D3 in different states of renal function, the fractional absorption of Ca45 (FCa45) and plasma calcium (PCa) were determined in rats with intact kidneys and in rats with reduced renal mass after 5/6 nephrectomy. The two series of experiments were performed in control animals, and in rats treated with: 1) 1,25(OH)2D3, 54 ng/rat/day, 2) 24,25(OH)2D3 in the same dose, and 3) 1,25 and 24,25(OH)2D3 in the same (and equal) doses. In all animals 1,25(OH)2D3 administration was associated with a significant increase in PCa and in FCa45. In rats with normal renal function, however, 24,25(OH)2D3 enhanced and in rats with reduced renal mass it suppressed the hypercalcemic effect of 1,25(OH)2D3. These variations in PCa were not associated with further alteration in FCa45 which was similar after 1,25(OH)2D3 and after combined 1,25 and 24,25(OH)2D3 in normal rats and in rats with chronic renal failure. FCa45 was found to be of the same magnitude in rats with normal renal function and in rats with reduced renal mass. These results confirm previous findings of normal intestinal absorption of Ca in mild to moderate renal failure. The above data suggest that 24,25(OH)2D3 used in an equivalent dose does not influence the intestinal effects of 1,25(OH)2D3. Therefore, the interaction of 1,25 with 24,25(OH)2D3 in rats with intact kidneys or with reduced renal mass occurs at extra-intestinal sites.

24,25-Dihydroxyvitamin D 3↗

PubMed1991

Postpartum hypercalcemia in a patient with medullary sponge kidneys.

Previous associations of primary hyperparathyroidism-induced hypercalcemia and medullary sponge kidney (MSK) have been reported. In this report, we describe a lactating woman MSK noted to be hypercalcemic throughout lactation, without evidence of hyperparathyroidism. After the baby was weaned, the serum calcium returned to normal. A bone biopsy performed while the patient was hypercalcemic was consistent with hyperparathyroidism, suggesting the presence of a parathyroid-like protein produced during lactation.

Adult↗

PubMed1991

A simple test of intestinal absorption of calcium in rats.

We have developed a simple test of fractional calcium absorption in rats using oral 45Ca. The tracer was administered via a gastric tube, each animal receiving 0.15 microgram 45Ca with calcium glubionate as a carrier. Plasma radioactivity was determined at 30, 60, 90 and 120 min and expressed as percent dose in extracellular fluid. The fractional absorption of 45Ca was also expressed as 'area under the curve' (F45Ca) calculated by Simpson's approximation for each rat. The fractional absorption of calcium was determined in fasting and nonfasting fed animal subsets, each subset including control and rats treated with 1,25(OH)2D3. After 1,25(OH)2D3 administration, a significant increase in plasma calcium was seen in both fasting and fed animals. The fractional absorption of calcium was significantly higher in 1,25(OH)2D3-treated fasting as compared with control rats. In these animals, a positive correlation was found between F45Ca and plasma calcium. In contrast, in fed rats, the determined fractional absorption of calcium was similar in control and after 1,25(OH)2D3 administration. These results point to the use of orally administered 45Ca as a technically easy method for calcium absorption which can be used in most laboratories. In fasting animals it is sensitive enough for the evaluation of the effect of promoters of calcium absorption. The different findings in fed and fasting states may be related to the transmural processes which regulate the intestinal absorption of calcium.

Animals↗

PubMed1991

Na,K-ATPase in isolated nephron segments in rats with experimental heart failure.

To characterize renal transport of Na+ in heart failure, urinary Na+ excretion (UNaV), aldosterone levels, and Na,K-ATPase activity in isolated nephron segments were determined in three groups: control rats, rats with heart failure and moderate sodium retention, and rats with heart failure and severe sodium retention. Heart failure was induced by a fistula between the aorta and vena cava. For the control group, UNaV was 0.66 +/- 0.04 (mean +/- SEM) mueq/min, and aldosterone was 18.4 +/- 3.5 ng%. Na,K-ATPase activity (in 10(-11) mol/mm/min) was 28.4 +/- 1.1 in the proximal convoluted tubule, 23.3 +/- 1.0 in the proximal straight tubule, 37.4 +/- 1.9 in the medullary thick ascending limb, 40.2 +/- 1.9 in the cortical thick ascending limb, 43.2 +/- 2.2 in the distal convoluted tubule, and 20.5 +/- 0.9 in the cortical collecting duct. For the group with moderate heart failure, UNaV was 0.35 +/- 0.02 (p less than 0.001 versus control), and aldosterone was 15.9 +/- 4.4 (p = NS versus control). Na,K-ATPase activity was unchanged in the proximal convoluted tubule, proximal straight tubule, medullary thick ascending limb, and cortical collecting duct, but it increased in the cortical thick ascending limb to 57.7 +/- 3.1 (p less than 0.001 versus control) and decreased in the distal convoluted tubule to 35.3 +/- 1.2 (p less than 0.005 versus control). For the group with severe heart failure, UNaV was 0.029 +/- 0.016 (p less than 0.001 versus control), and aldosterone was 186.0 +/- 14.8 (p less than 0.001 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Hyponatremia induced by exercise: a 24-hour endurance march study.

In our previous studies on the relationship between prolonged physical stress and muscle enzyme activities, a number of individuals suffered a hyponatremic state. The present study was conducted to evaluate the effect of prolonged physical stress on the development of hyponatremia. Seventeen physically fit male subjects were studied during a 24-hour endurance march. Serum sodium, that averaged 142 +/- 2 before the march, decreased during the march to 135 +/- 2 mEq/l (p less than 0.01 versus before the march). Blood and plasma volumes increased by 8 and 16% (p less than 0.05), respectively. Creatinine clearance before the march declined from 118 +/- 24 to 74 +/- 19 ml/min (p less than 0.005) during the march and correlated negatively with serum sodium (p less than 0.002; r = 0.59). Urinary sodium excretion before the march was 132 +/- 55 and during the march was 123 +/- 62 mEq/24 h. Free water clearance rose during the march and correlated negatively with serum sodium (p less than 0.001), suggesting an appropriate renal diluting response. However, the fall in serum sodium correlated positively with water intake (p less than 0.01; r = 0.59). These results show that hyponatremia develops during endurance marching in normal subjects on an unrestricted high water intake. The renal response to water intake is appropriate; however, the subjects fall to produce maximally diluted urine. Therefore, we suggest that water intake should follow physiological needs and not forced to cause hyponatremia during prolonged physical stress.

Adult↗

PubMed1990

Effect of indomethacin in vivo and PGE2 in vitro on MTAL Na-K-ATPase of the rat kidney.

We have previously shown that prostaglandin synthesis inhibition in rats which reduces urinary excretion of PGE2 and sodium, is associated with increased Na-K-ATPase activity in renal medulla. To further characterize this interaction studies were performed in isolated segments of medullary thick ascending limb of Henle's loop (MTAL) in rats. The effect of pretreatment with indomethacin in vivo and incubation with PGE2 in vitro on MTAL Na-K-ATPase activity was studied. Pretreatment of rats with indomethacin increased Na-K-ATPase of the MTAL from 37.2 +/- 2.0 x 10(-11) mol/mm/min in controls to 62.7 +/- 2.2 (p less than 0.001) while Mg-ATPase was only slightly decreased. Incubation of MTAL Na-K-ATPase from indomethacin pretreated rats with increasing concentration of PGE2 in vitro dose dependently inhibited MTAL Na-K-ATPase activity with no effect on Mg-ATPase. Baseline Na-K-ATPase was 62.7 +/- 2.2 in MTAL from indomethacin pretreated rats and decreased to 36.9 +/- 1.4 (p less than 0.001) with 1 microM of PGE2, to 26.5 +/- 2.3 (p less than 0.001) with 10 microM PGE2 and to 22.0 +/- 1.0 (p less than 0.001) with 100 microM PGE2. 100 microM PGE2 in the incubation medium inhibited MTAL Na-K-ATPase of intact rats from 37.2 +/- 2 to 21.3 +/- 1.2 (p less than 0.001) and completely abolished the indomethacin induced increase in MTAL Na-K-ATPase. The results of this study show stimulation of MTAL Na-K-ATPase by pretreatment with indomethacin in vivo and, direct inhibition of MTAL Na-K-ATPase by PGE2 in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Renal sodium handling and stimulation of medullary Na-K-ATPase during blockade of prostaglandin synthesis.

The effect of suppression of prostaglandin synthesis on renal sodium handling and microsomal Na-K ATPase was studied in control and indomethacin treated intact rats maintained on a normal sodium diet (series A) and chronically salt loaded (series B). Indomethacin administration resulted in a decreased GFR and a significantly depressed urinary excretion and an increased fractional reabsorption of sodium in animals fed the normal sodium diet or chronically salt loaded. In rats maintained on a normal Na diet, the activity of the renal medullary Na-K ATPase after indomethacin was 206.3 +/- 6.4 ug Pi/mg protein, i.e. significantly higher as compared with the enzyme activity in the medullary renal fraction from control animals in which it averaged 148 +/- 7.79 ug Pi/mg protein (p less than 0.001). While after chronic salt load a similar increment in the activity of renal medullary Na-K ATPase was observed, no additional stimulation was elicited by subsequent indomethacin administration. The addition of exogenous PGE2, 0.1 mM to microsomal fractions obtained from kidneys of normal rats, was associated with a moderate suppression of the medullary Na-K-ATPase activity, from a basal level of 170 +/- 16 to 151.3 +/- 13 umol Pi/mg protein/hr (p less than 0.005). In isolated segments of medullary thick ascending limb of Henle's loop (MTAL) addition of PGE2 to the incubation medium resulted in a significant inhibition of Na-K ATPase from 37.2 +/- 2 to 21.25 +/- 1.17 x 10(-11) mol/mm/min (p less than 0.0001). These findings suggest that the increased renal Na reabsorption after inhibition of PG synthesis might be related, at least partly, to stimulation of medullary Na-K ATPase. In parallel, the reported natriuretic effect of prostaglandins might imply a direct inhibitory effect of these mediators on renal Na-K ATPase.

Animals↗

PubMed1990

Reduced Na-K-ATPase in distal nephron in glycerol-induced acute tubular necrosis.

To further characterize changes in tubular Na-K-ATPase in acute tubular necrosis (ATN), segmental analysis was performed in rat nephrons. Na-K-ATPase was assayed in the following segments: proximal convolution (PC), proximal straight (PS), outer medullary thick ascending limb (MTAL), cortical thick ascending limb (CTAL), distal convolution (DC) and cortical collecting duct (CCD) in three groups of rats: 1.) intact; 2.) moderate non-oliguric ATN; and 3.) severe oliguric ATN. GFR and CNa/GFR X 100 were in group 1 0.80 +/- 0.05 ml/min and 0.68 +/- 0.06, in group 2 0.14 +/- 0.02 and 1.46 +/- 0.35, and in group 3 0.04 +/- 0.01 and 0.46 +/- 0.15, respectively. Na-K-ATPase in PC and PS were similar in all three groups. Na-K-ATPase levels were in MTAL: in group 1 37 +/- 2 X 10(-11) mol/mm/min, in group 2 20 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 24 +/- 2 X 10(-11), P less than 0.001 versus group 1. In CTAL Na-K-ATPase levels were: in group 1 40 +/- 2 X 10(-11), in group 2 33 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 27 +/- 2 X 10(-11), P less than 0.001 versus groups 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

PubMed1990

Glycerol-induced acute renal failure in the rat: the protective effect of unilateral nephrectomy.

Studies were performed to evaluate the effect of unilateral nephrectomy on glycerol-induced acute renal failure in the rat. Normal rats were subjected to either sham uninephrectomy (n = 43) or right uninephrectomy (n = 53). The functional compensation of the remaining kidney was followed after 1 and 2 weeks. Fourteen days after the operation, acute renal failure was induced by injection of 50% glycerol solution to both groups. Uninephrectomised rats developed a lesser degree of renal failure compared to sham-operated rats. Forty-eight hours after glycerol injection, PCr of uninephrectomised rats was 260 +/- 22 mumol/l compared with 338 +/- 26 in sham-operated rats (P less than 0.0125) and CCr in uninephrectomised rats was greater (0.10 +/- 0.01 ml/min vs 0.07 +/- 0.01; P less than 0.025) in sham rats. Uninephrectomised rats had significantly greater recovery of CCr compared to sham rats at 24 h (20.1% +/- 2.3 vs 13.1% +/- 2.2, P less than 0.025) and at 48 h (32.1% +/- 3.3 vs 19.2% +/- 3.3, P less than 0.005) after glycerol injection. FENa was significantly less in uninephrectomised rats: 0.96 +/- 0.16% vs 2.25 +/- 0.05% (P less than 0.025) in sham rats 24 h post glycerol. Urinary excretion of K+ was greater in rats following uninephrectomy compared to sham rats both after 24 h and 48 h post glycerol (P less than 0.01), accompanied by lower plasma potassium (P less than 0.05). A correlation coefficient (r) of 0.793 was observed between urinary potassium excretion rate and percentage recovery of CCr.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

PubMed1990

The influence of 24,25(OH)2D3 on the calcemic effect of 1,25(OH)2D in rats with chronic renal failure is parathyroid hormone dependent.

Previous studies from our laboratory have shown that 24,25(OH)2D3 attenuates the calcemic effect of 1,25(OH)2D3 in rats with reduced renal mass. This study was undertaken to clarify the role of parathyroid hormone in this response. Adult rats (n = 27) with reduced renal mass after parathyroidectomy with an initial plasma calcium of 3.7 +/- 0.1 mEq/liter were divided into four groups: (i) control rats and rats treated with (ii) 24,25(OH)2D3, (iii) 1,25(OH)2D3, and (iv) both 1,25 and 24,25(OH)2D3. After 4 days significant hypercalcemia was seen in PTX animals receiving 1,25(OH)2D3 alone or in combination with 24,25(OH)2D3. Plasma calcium in the combined therapy rats (7.42 +/- 0.22 mEq/liter) was significantly higher than in those treated with 1,25(OH)2D3 alone (6.68 +/- 0.22 mEq/liter, P less than 0.05). After 8 days, plasma calcium was higher in the rats treated with 1,25(OH)2D3 but was of same magnitude in those treated with 1,25(OH)2D3 alone or in combination with 24,25(OH)2D3. In contrast, in a subset of rats (n = 35) with reduced renal mass but intact parathyroid glands similarly treated with the vitamin D metabolites, a blunted calcemic response was seen after the combination of 1,25(OH)2D3 with 25,25(OH)2D3 administration alone. These results show that in rats with reduced renal mass, 24,25(OH)2D3 attenuates the calcemic effect of 1,25(OH)2D3 only in the presence of intact parathyroid glands. The different calcemic responses to 1,25 or combined 1,25 and 24,25(OH)2D3 in intact or parathyroidectomized rats with chronic renal insufficiency may result from different interaction between the vitamin D metabolites and the parathyroid hormone, presumably at the level of bone.

24,25-Dihydroxyvitamin D 3↗

PubMed1990

Opposite effects of diabetes on nephrotoxic and ischemic acute tubular necrosis.

The effect of streptozotocin-induced diabetes mellitus on two different models of acute tubular necrosis (ATN), was studied: (i) the nephrotoxic model of HgCl2-induced ATN and (ii) the ischemic model of renal artery clamping for 60 min. Induction of ATN with HgCl2 in normal rats decreased CrCl from 0.67 +/- 0.05 to 0.1 +/- 0.019 ml/min (P less than 0.001) after 24 hr, and it deteriorated further to 0.03 +/- 0.013 ml/min after 48 hr; whereas, in the diabetic rats, HgCl2 decreased CrCl from 0.98 +/- 0.11 only to 0.31 +/- 0.037 ml/min (P less than 0.0001), but CrCl recovered to 0.50 +/- 0.08 ml/min after 48 hr. Bilateral clamping of renal arteries for 60 min in control and diabetic rats extremely decreased CrCl in both groups. Twenty-four hours after clamping, two of nine rats from the diabetic group died, whereas none from the control group died. Forty-eight hours after clamping, all nine rats from the diabetic group died, whereas only two rats from the control group died, and in the four surviving rats CrCl recovered slightly. Our study shows that streptozotocin-induced diabetes could not confer a general protection against ATN. It was protective against a nephrotoxic insult but aggravated the ischemic insult. An attempt to reconcile these discrepant effects is made in the Discussion.

Acute Kidney Injury↗

PubMed1990

25-Hydroxycholecalciferol and 1,25-dihydroxycholecalciferol enhances phosphaturia in rats with reduced renal mass: evidence for a PTH-dependent mechanism.

To evaluate the acute effect of 25-hydroxycholecalciferol [25(OH)D3] on renal handling of phosphate in rats with reduced renal mass, clearance studies were performed in the following groups of five sixth (5/6) nephrectomized (NPX) animals: (1) rats with intact parathyroids infused 25(OH)D3 (5/6 NPX + 25(OH)D3), (2) rats with intact parathyroids which received the vitamin D vehicle only (5/6 NPX). A separate subgroup of animals received 1,25-dihydroxycholecalciferol [1,25(OH)2D3] [5/6 NPX + 1,25(OH)2D3], (3) parathyroidectomized (PTX) rats infused 25(OH)D3 [5/6 NPX-PTX + 25(OH)D3], and (4) PTX rats infused the vehicle only (5/6 NPX-PTX). In group 1 [5/6 NPX + 25(OH)D3] the final fractional excretion of phosphate (CP/CIn) was significantly higher, i.e., 0.281 +/- 0.016, as compared to that of control animals (group 2, 5/6 NPX) in which the final CP/CIn averaged 0.195 +/- 0.016 (p less than 0.005). There was no difference, however, in the urinary cAMP excretion between these two groups. A similar phosphaturic effect was seen in rats infused 1,25(OH)2D3. After parathyroidectomy, however, the final CP/CIn was similar in rats receiving 25(OH)D3 [group 3, 5/6 NPX-PTX + 25(OH)D3] and in those receiving the vehicle alone (group 4, 5/6 NPX-PTX). In vitro studies on renal cortical adenylate cyclase activity in kidney remnants from the rats with reduced renal mass failed to demonstrate blunting of PTH activation of the enzyme by 25(OH)D3 or by 1,25(OH)2D3 as seen in kidneys from the control intact animals. These experiments demonstrate a phosphaturic response to 25(OH)D3 without parallel change in urinary cAMP in 5/6 NPX with intact parathyroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

PubMed1989

Inhibition of thick ascending limb Na+-K+-ATPase activity in salt-loaded rats by furosemide.

To evaluate the role of increased thick ascending limb Na+-K+-ATPase activity in rats undergoing hypertonic salt loading, the following groups of rats were studied: 1) control rats, 2) rats receiving an oral hypertonic Na load for 7 days, and 3) rats receiving the same oral Na load as in group 2 plus a daily injection of 10 mg/100 g of furosemide ip for 7 days. Salt loading (group 2) was associated with increased glomerular filtration rate (GFR) and hence an increased filtered load of sodium. Plasma aldosterone levels were markedly decreased. Na+-K+-ATPase was unchanged in the proximal tubule [convoluted (PC) and straight (PS)], increased in the thick ascending limb of Henle's loop [outer medullary (OMTAL) and cortical (CTAL)] and decreased in the distal nephron [distal convoluted tubule (DCT) and cortical collecting duct (CCD)]. The renal corticomedullary gradient of solutes was markedly increased in the salt-loaded group. Salt loading plus furosemide for 7 days (group 3) was associated with severe dehydration and hypernatremia. GFR as well as plasma aldosterone levels were unchanged compared with control. Na+-K+-ATPase was significantly increased in the proximal tubule (PC and PS), markedly decreased in the thick ascending limb of Henle's loop (OMTAL and CTAL), increased in the DCT and unchanged in the CCD. The increase in the corticomedullary gradient caused by salt loading per se was abolished by treatment of salt-loaded rats with furosemide. These results indicate that treatment with furosemide prevents the preservation of water balance and of normal body fluid tonicity in rats undergoing hypertonic Na loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗