Effect of chlorothiazide on renal calcium and magnesium handling in the hamster

1982 ◽  
Vol 60 (9) ◽  
pp. 1160-1165 ◽  
Author(s):  
Norman L. M. Wong ◽  
Gary A. Quamme ◽  
John H. Dirks

Recollection micropuncture and clearance studies were performed on 21 thyroparathyroidcetomized hamsters to characterize the effect of chlorothiazide on tubular sodium, calcium, and magnesium transport. Acute administration of chlorothiazide resulted in a marked natriuresis while urinary calcium excretion fell and magnesium remained unchanged. The fraction of sodium, calcium, and magnesium remaining at the late proximal tubule increased modestly from 65 ± 4 to 75 ± 3, 68 ± 3 to 75 ± 4, and 78 ± 4 to 85 ± 2%, respectively. Distal tubular fluid to ultrafilterable plasma (TF/UF) sodium concentration rose from 0.24 ± 0.03 to 0.44 ± 0.04 whereas distal TF/UFCa concentration fell from 0.58 ± 0.05 to 0.38 ± 0.06. The fraction of sodium remaining at the distal tubule rose from 4.0 ± 1.4 to 10.0 ± 1.4% while that of calcium decreased from 10.2 ± 1.1 to 7.6 ± 1.2% following administration of chlorothiazide. No change was observed in distal delivery of magnesium. Thus chlorothiazide acted in the distal tubule to decrease sodium reabsorption, enhance calcium transport, and had little effect on distal magnesium reabsorption. These data are consistent with the distal tubular action of chlorothiazide which is independent of parathyroid hormone.

1981 ◽  
Vol 59 (2) ◽  
pp. 122-130 ◽  
Author(s):  
Gary A. Quamme

Superficial nephrons were perfused in vivo to determine the effect of intraluminal sulfate (1–20 mM) on electrolyte reabsorption in the rat with special reference to calcium and magnesium transport. This technique allowed us the opportunity of investigating separate electrolyte transfers without alteration of extrarenal influences. The major amount of perfused sulfate was absorbed in the proximal tubule with little absorption distal to the late proximal collection site. Phosphate transport was not affected by high luminal sulfate concentrations indicating distinct reabsorptive mechanisms for these two anions. Intraluminal sulfate significantly inhibited calcium and magnesium reabsorption in the proximal tubule, loop of Henle, and superficial distal tubule, in distinction to modest effects on sodium transport in these nephron segments. Chloride transport was not altered. The inhibition of divalent cation transfer was not quantitively similar in the different tubule segments. Small amounts of sulfate completely inhibited proximal calcium and magnesium reabsorption with little effect on transport within the loop of Henle. Enhanced distal delivery of sulfate significantly inhibited calcium and magnesium reabsorption in the distal tubule, a site where the sulfate anion is not reabsorbed. These results demonstrate the importance of distal delivery of anionic ligands capable of forming nonreabsorbable complexes. Thus distal calcium and magnesium transport may be greatly modified by proximal control of anion reabsorption.


1969 ◽  
Vol 47 (7) ◽  
pp. 619-626 ◽  
Author(s):  
A. Gonda ◽  
N. Wong ◽  
J. F. Seely ◽  
J. H. Dirks

The effects of unilateral vasodilatation and alterations in the mean arterial pressure upon the renal handling of calcium and magnesium were studied by clearance methods in dogs. Unilateral vasodilatation was produced by infusion of acetylcholine or bradykinin into the left renal artery, while arterial pressure was altered by aortic constriction, carotid occlusion and vagotomy, or by systemic infusion of angiotensin. Urinary electrolyte excretion was increased markedly by the infusion of each vasodilator and also varied directly with the mean arterial pressure, despite the absence of any significant changes in the filtered load. The fractional excretion of both calcium and magnesium correlated significantly with that of sodium. These results indicate that acute changes in renal hemodynamics modify the tubular reabsorption of divalent cations as well as alter sodium reabsorption.


1980 ◽  
Vol 238 (6) ◽  
pp. E573-E578 ◽  
Author(s):  
G. A. Quamme

Renal calcium and magnesium reabsorption was investigated in young, thyroparathyroidectomized rats receiving synthetic salmon calcitonin. Kidney and tubular function was assessed by clearance and in vivo microperfusion techniques, respectively. Calcitonin reduced urinary calcium and magnesium excretion that was attributed to increased reabsorption within the loop of Henle. This enchanced reabsorption was independent of parathyroid hormone; however, it is contingent on a decline in plasma calcium concentration. Prevention of hypocalcemia by CaCl2 infusion in rats acutely administered calcitonin resulted in loop function comparable to animals not receiving the hormone. Calcitonin had little effect on proximal tubule or distal tubule electrolyte reabsorption. These results are consistent with a transport model for calcium and magnesium in the loop of Henle involving a contraluminal transfer step modulated by absolute extracellular calcium or magnesium. Furthermore, these studies suggest that the discrepancies present in the literature concerning renal effects of calcitonin on electrolyte reabsorption are due to variations in observed hormone action, namely, the effect on plasma calcium concentration.


1979 ◽  
Vol 236 (4) ◽  
pp. F342-F348 ◽  
Author(s):  
C. A. Harris ◽  
M. A. Burnatowska ◽  
J. F. Seely ◽  
R. A. Sutton ◽  
G. A. Quamme ◽  
...  

Recollection micropuncture and clearance studies were carried out on thyroparathyroidectomized hamsters to clarify the localization of the effects of parathyroid hormone (PTH) on renal electrolyte transport. The clearance data confirmed that PTH inhibits phosphate and enhances calcium and magnesium reabsorption. These effects appeared to result from actions of the hormone in several parts of the nephron. In the proximal tubule PTH did not affect H2O reabsorption but inhibited phosphate reabsorption ((TF/P)PO4 increased from 0.46 +/- 0.04 to 0.57 +/- 0.03, P less than 0.02) and appeared to enhance calcium and magnesium reabsorption ((TF/UF)Ca decreased from 1.41 +/- 0.07 to 1.25 +/- 0.06, P less than 0.001, and (TF/UF)Mg from 1.66 +/- 0.10 to 1.51 +/- 0.08, P less than 0.05; in control animals (TF/UF)Ca increased from 1.51 +/- 0.10 to 1.65 +/- 0.11, P less than 0.01). PTH further inhibited phosphate reabsorption and enhanced calcium and magnesium reabsorption between the late proximal and early distal sites of puncture. Comparison of fractional deliveries of calcium and magnesium from the late distal tubule with their fractional excretions suggests an additional effect beyond the distal puncture site. The phosphaturic, but not the calcium- and magnesium-retaining, effects of PTH were abolished by a 16-h fast.


1970 ◽  
Vol 39 (5) ◽  
pp. 605-623 ◽  
Author(s):  
A. Z. Györy ◽  
K. D. G. Edwards ◽  
J. Robinson ◽  
A. A. Palmer

1. The association of varying levels of urinary pH, urinary citrate and urinary calcium and magnesium excretion rates with kidney citrate, calcium and magnesium concentrations in experimental nephrocalcinosis was examined in twenty-four rats in a 3 × 2 multifactorial experiment with four replicates. All rats received the same synthetic diet for 6 weeks before being killed in the seventh week. In addition the rats received calcium supplements as calcium chloride (diet A), calcium carbonate (diet B), or as an equal mixture of calcium chloride and carbonate (diet N), the content of calcium being kept constant at 6·3 mg per g of diet for all rats. Half of the rats also received 2·5 mg of acetazolamide per g of diet. 2. Diet A produced a systemic acidosis and the most acid urinary pH. Diet B plus acetazolamide produced a more severe systemic acidosis and the most alkaline urinary pH. Urinary magnesium, citrate and calcium excretion rates were generally reduced below normal. Urinary excretion of magnesium and calcium were significantly higher in those rats on diet A than in those on diet B, while urinary citrate excretion was highest in the latter. Acetazolamide caused a further increase in urinary calcium excretion but a decrease in urinary magnesium and citrate excretions. 3. Acetazolamide significantly reduced plasma calcium but elevated plasma magnesium. The changes produced in plasma and urinary calcium and magnesium in the present study were consistent with an action through systemic acidosis for calcium and through urinary pH for magnesium, both being effected at a tubular site. 4. Variation in diet alone as well as acetazolamide administration were significantly associated with variation in the degree of nephrocalcinosis (P < 0·05 and P < 0·005 respectively). Acetazolamide increased nephrocalcinosis by a factor of at least 10. Analysis of covariance showed that acetazolamide was no longer associated with significant nephrocalcinosis when its effects on urinary pH and magnesium were removed from its effect on nephrocalcinosis. Removal of the effect of acetazolamide on urinary citrate excretion did not alter the effect of acetazolamide in producing nephrocalcinosis. Although urinary citrate was reduced to below 10% of normal whenever nephrocalcinosis was severe, it was also reduced to below 10% in rats on diet A which had normal kidney tissue calcium content, the most acid urinary pH and the highest urinary magnesium. 5. Elevation of urinary pH and reduction in urinary magnesium excretion were therefore considered to be of major importance in the causation of experimental nephrocalcinosis; reduction in urinary citrate excretion appeared to be only of secondary importance.


1988 ◽  
Vol 75 (2) ◽  
pp. 203-207 ◽  
Author(s):  
Viroon Mavichak ◽  
Christopher M. L. Coppin ◽  
Norman L. M. Wong ◽  
John H. Dirks ◽  
Valerie Walker ◽  
...  

1. The renal handling of calcium and magnesium was studied in six patients with persistent hypomagnesaemia after cis-platinum treatment for testicular tumours. 2. In comparison with normal subjects, the patients showed hypomagnesaemia (mean 0.54 mmol/l), which was associated with a normal urinary magnesium excretion (mean 4.83 mmol/24 h). Urinary calcium excretion was significantly lower in the patients than in the normal subjects (mean 2.05 vs 5.15 mmol/24 h, respectively; P < 0.01), despite slightly higher total serum calcium levels (2.53 vs 2.38 mmol/l, respectively; P < 0.05). During magnesium chloride infusion, when serum magnesium levels were comparable in patients and controls, urinary calcium excretion remained lower in the patients, indicating that hypomagnesaemia was not the cause of the hypocalciuria. 3. Dietary magnesium supplementation resulted in a significant increase in the serum magnesium levels in the patients, while dietary magnesium deprivation resulted in a comparable decrease in urinary magnesium excretion in patients and controls (to 1.46 and 2.00 mmol/day, respectively), although the serum magnesium level fell further (to 0.46 mmol/l) in the patients. 4. The dissociation of renal calcium and magnesium excretion appears to be part of the intrinsic tubular defect caused by cis-platinum. This dissociation of urinary calcium and magnesium excretion, which resembles that seen in Bartter's syndrome, may result from a lesion in the distal convoluted tubule.


1975 ◽  
Vol 228 (4) ◽  
pp. 1262-1268 ◽  
Author(s):  
RN Khuri ◽  
N Strieder ◽  
M Wiederholt ◽  
G Giebisch

Sodium transport was studied across proximal and distal tubules of rats undergoing progressive intravenous loading with either isomotic saline or urea (200 mosmol)-saline (100 mosmol) solutions. Free-flow as well as recollection micropuncture techniques were used, and tubular fluid (TF) samples were analyzed for inulin-14C and sodium (Na). With administration of progressively larger intravenous saline loads, the delivery of fluid and sodium into the distal tubule rose. Concomitantly, the normally observed decline of tubular sodium concentrations along the distal tubule became attenuated until it was abolished at the highest infusion rates of saline solutions. Absolute reabsorption rates of Na across the distal tubule increased in proportion to tubular flow rate, and no tubular maximum (Tm) was observed. It is suggested that the delivery of increased amounts of sodium to the normally unsaturated later parts of the distal tubule and the elevated tubular sodium concentration after saline loading account for the observed stimulation of distal tubular net sodium transport. The extent of transport stimulation is also subject to control by the amount of urea accumulation along the distal tubule. As the latter declines, sodium reabsorption is proportionately enhanced.


1969 ◽  
Vol 51 (3) ◽  
pp. 575-589
Author(s):  
A. P. M. LOCKWOOD ◽  
J. A. RIEGEL

1. Measurements have been made of the concentrations of sodium, calcium and magnesium in the blood and urine of Carcinus maenas after transfer to 50 or 150% sea water. Inulin clearance studies were also made. 2. Magnesium is concentrated in the urine by a secretory process when the crabs are in 100% sea water or 150% sea water. There is evidence that the rate of secretion declines when the crabs are in 50% sea water or in 100% magnesium-free sea water. 3. There is no evidence for active withdrawal of magnesium from the urine. When the blood is depleted of this ion the U/B for magnesium drops to a value similar to the U/B for inulin. 4. The clearance of inulin is faster when Carcinus is in 150% sea water than when it is in 100% sea water, and it is calculated that the animal excretes magnesium at a faster rate than it does in 50% sea water. 5. The excretion of magnesium by Carcinus and Pachygrapsus is compared, and it is shown that magnesium is conserved more effectively in dilute media by Carcinus than by Pachygrapsus. This probably reflects differences in the ecology of the two species.


1981 ◽  
Vol 241 (5) ◽  
pp. F487-F494 ◽  
Author(s):  
D. K. Abu-Hamdan ◽  
S. D. Migdal ◽  
R. Whitehouse ◽  
P. Rabbani ◽  
A. S. Prasad ◽  
...  

Zinc clearance studies in anesthetized dogs were performed during hydropenia, mannitol infusion, and infusion of mannitol plus ZnSO4, ZnCL2, or cysteine. Mannitol expansion caused no significant change in Zn clearance. ZnSO4 infusion increased filtered Zn 13-fold without changing clearance. Zn excretion increased only sixfold, indicating increased net Zn reabsorption. Cysteine infusion increased urinary Zn excretion 86-fold, indicating net tubular Zn secretion, some of which derived from nonplasma sources. Stop-flow studies localized Zn reabsorption to the distal nephron during infusion of mannitol and mannitol plus ZnSO4 or ZnCl2. Net Zn secretion was shown to occur in the proximal tubule during cysteine infusion with reversal of the distal reabsorption pattern seen during ZnSO4 and ZnCl2 infusion. Despite increased urinary Zn excretion during ZnSO4 infusion, calcium excretion was unaltered. During cysteine infusion dissociation of tubular handling of CA2+ and Zn occurred in both the proximal and distal tubule. These experiments demonstrate that the nephron under these experimental conditions is capable of both proximal secretion and distal reabsorption of Zn.


1970 ◽  
Vol 64 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Lars Runeberg ◽  
B.-A. Lamberg ◽  
P. Reissell ◽  
H. Adlercreutz

ABSTRACT The time course of the renal excretion of calcium, magnesium, sodium, and potassium during sodium depletion and the rapid correction of the extracellular volume deficit was studied in normal subjects and in patients with Addison's disease (AD). The decrease in body weight was similar in the two groups, but the haematocrit value increased more in the patients with AD. Sodium depletion suppressed sodium excretion much more efficiently in normal controls than in the AD patients. Calcium excretion was roughly equally depressed in two groups. During sodium loading there was an immediate increase in renal sodium excretion in the patients with AD, whereas the sodium-retaining state generally continued for about one day in the normal controls. Urinary potassium decreased gradually during the first day of sodium loading in the normal controls but not in the AD patients. In the normal subjects calcium excretion remained low during the first day and increased on the second day of sodium loading. In the AD patients there was a gradual increase in urinary calcium during the first day of sodium loading, which did not, however, parallel the changes in urinary sodium content in individual urine samples. Urinary magnesium did not change significantly. It is concluded that the effect of adrenal steroids on renal calcium excretion is of minor importance. They may, however, to some extent induce calcium retention.


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