TPTX Rats Research Articles

Evidence that resistance to the calcemic action of parathyroid hormone in rats with acute uremia is caused by phosphate retention

An animal model was developed to examine the cause of resistance to the calcemic action of PTH in renal failure. Thyroparathyroidectomized (TPTX) rats were repeatedly reinfused with their excreted urine, over a 5-hour period, to produce an acute uremic animal with normal kidneys. Nonuremic controls were infused with equivalent volumes of a simple electrolyte solution. Using this model, we have demonstrated impaired calcemic response to PTH (Lilly Parathyroid Extract, 80 U/100 g) in urine-infused rats compared with electrolyte-infused rats. The final plasma calcium concentrations were 12.0 +/- 0.3 and 14.9 +/- 0.3 mg/dl, respectively (P less than 0.001). The cause of this impaired calcemic response was investigated by reinfusing rats with their own urine that had been pretreated with either activated charcoal or zirconium oxide in two different anionic forms, or urine that had been ultrafiltrated through an Amicon membrane of which the stated molecular-weight cut-off of the smallest pore-size membrane was 500 daltons. It was found that charcoal and ultrafiltration techniques had no effect, whereas the zirconium oxide treatment completely corrected the impaired calcemic response and returned the plasma phosphorus to a concentration similar to that in nonuremic controls. This can be explained by the fact that the principal effect of zirconium oxide on urine is to remove inorganic phosphate. Other groups of TPTX rats given PTH extract were infused with an electrolyte solution containing varying amounts of phosphate up to a maximum similar to the amount that a urine-infused rat would receive. A highly significant inverse relationship was found between the dose of phosphate infused with the electrolyte solution and the measured calcemic response to PTH. This relationship is represented by the following equation: calcium (mg/dl) = 14.84 - 0.139 inorganic phosphate; r = 0.915, P less than 0.001. From these series of studies, we conclude that phosphate retention is the cause of resistance to the calcemic action of PTH extract in this acute uremic model.

Endogenous nature of circadian rhythms in calcium metabolism.

Rats studied when the lights are on from 0600 to 1800 daily and fed only in the dark period displayed circadian rhythms in plasma calcium (ionized and total) and 45Ca concentrations, 6 and 8 days after 45Ca administration. In rats fed a calcium-deficient diet, the amplitude of daily variation of plasma ionized and total calcium increased markedly whereas plasma 45Ca daily fluctuation remained essentially unchanged. In the calcium-deficient rats, significant correlations between plasma calcium and 45Ca and between plasma calcium and magnesium were observed throughout the 24 h; circadian periodicity of calcium metabolism persisted in rats fasted overnight, regardless of the illumination schedule. Normal daily fluctuations in plasma 45Ca, lost after thyroparathyroidectomy (TPTX), were restored by feeding the TPTX rats a high-calcium diet. These results demonstrate clearly that circadian rhythms of calcium metabolism occurred irrespective of the light-dark schedule, the calcium supply through intestines and the thyroparathyroid system. An attractive suggestion is that circadian rhythmicity originates as a result of dynamic properties involving nonlinear processes of calcium metabolism.

Phosphate transport along the inner medullary collecting duct of the rat.

The question of phosphate transport along the collecting duct remains controversial inasmuch as no data from direct in vivo evaluation of this nephron segment have been reported. We measured net phosphate transport along the inner medullary collecting duct (IMCD) using the collecting duct microcatheterization technique in five groups of rats. In control rats no net phosphate transport was found and 9.4% of the fraction of filtered phosphate (FFP) entered the IMCD and was excreted. After acute thyroparathyroidectomy (TPTX) there was a striking reduction in the FFP entering the IMCD, 1.8%, and significant reabsorption occurred, 0.5% being excreted. With acute TPTX and parathormone infusion, delivery increased to 33% without significant change along the IMCD. With acute TPTX and phosphate infusion, delivery was increased to control levels but no change was found in net phosphate transport. In rats studied 5-7 days after uninephrectomy alone, phosphate delivery was greater than in control, 25%, and no net phosphate transport was found. These studies demonstrate that phosphate absorption occurs along the IMCD in acutely TPTX rats when the delivery of phosphate to the IMCD is markedly reduced. The increase in phosphaturia which occurs after a reduction in renal mass cannot be accounted for by changes in net phosphate transport along the IMCD.

An extrarenal role for parathyroid hormone in the disposal of acute acid loads in rats and dogs.

Acid infusion studies were performed in nephrectomized rats and dogs with either intact parathyroid glands (intact) or after thyroparathyroidectomy (thyroparathyroidectomized [TPTX]) to determine the role of parathyroid hormone (PTH) in extrarenal disposal and buffering of acutely administered acid. 29 intact rats given 5 mM/kg HCl and 6 intact dogs given 7 mM/kg HCl developed severe metabolic acidosis but all survived. However, each of 12 TPTX rats and 4 TPTX dogs given the same acid loads died. Intact rats and dogs buffered 39 and 50% of administered acid extracellularly, respectively, whereas extracellular buffering of administered acid was 97 and 78% in TPTX rats and dogs, respectively. 17 TPTX rats and 6 TPTX dogs given synthetic PTH 2 h before acid infusion survived. The blood bicarbonate and extracellular buffering in these animals, measured 2 h after acid infusion, was similar to intact animals. Changes in liver, heart, and skeletal muscle pH determined from [(14)C]5,5-dimethyl-2,4 oxazolidinedione distribution seemed insufficient to account for the increased cell buffering of PTH-replaced animals. Indeed, muscle pH in TPTX dogs given PTH and acid was only 0.06 pH units lower than in control dogs given no acid, suggesting that another tissue, presumably bone, was the target for PTH-mediated increased cell buffering. This conclusion was supported by the observation that PTH did not alter the pH of intact rat diaphragms in vitro. These results indicate that PTH is necessary for the optimal buffering of large, acute acid loads presumably by increasing bone buffering.

Renal handling of calcium: influence of parathyroid hormone and 1,25-dihydroxyvitamin D3

The influence of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the renal Ca handling was studied in vitamin D-replete rats. The relation between plasma concentration ([Ca]P) and urinary Ca (UCaV/ml GF) was ascertained by clearance techniques over the [Ca]P range of 1.4-3.4 mM varied by infusion of Ca gluconate. Chronic thyroparathyroidectomy (TPTX) decreased the plasma Ca threshold from about 2.3 to 1.5 mM. Between [Ca]P 1.4 and 3.4 mM there was a linear increase in UCaV/ml GF corresponding to 35-50% of the increment in filtered load. In TPTX, PTH (2.5 IU/h i.v.) shifted the Ca threshold from 1.5 to 2.3 mM, without changing the slope of UCaV/ml GF on [Ca]P. The effect of TPTX on the renal Ca handling was not corrected by doses of 1,25(OH)2D3, which increased the intestinal Ca absorption of TPTX rats to normal level. In intact and TPTX rats disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) given at doses which inhibit the production of 1,25(OH)2D3 did not change the tubular Ca handling. Furthermore, 1,25(OH)2D3 had no effect in EHDP-treated TPTX rats. Therefore, tubular Ca handling does not appear to be altered in response to chronic endogenous variation or physiologic supplementation of 1,25(OH)2D3 in vitamin D-replete rats. This is in contrast to the marked alteration observed after TPTX or PTH administration.

Resistance to the phosphaturic and calcemic actions of parathyroid hormone during phosphate depletion. Prevention by 1,25-dihydroxyvitamin D3.

Recent observations indicate that in thyroparathyroidectomized (TPTX) rats fed a low (0.2 g/100 g) phosphorus diet, the tubular phosphaturic response to parathyroid hormone (PTH) remains markedly blunted even when it is assessed at normal or high plasma concentration and filtered load of inorganic phosphate (Pi). Because 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] decreases the tubular capacity to reabsorb Pi when chronically administered to TPTX rats, we have studied whether this vitamin D(3) metabolite could specifically increase the phosphaturic response to PTH in phosphate-deprived animals. The results show that in Vitamin D-replete TPTX rats fed a low (0.2 g/100 g) phosphorus diet, 1,25(OH)(2)D(3) (2 x 13 pmol/d i.p. for 7 d) markedly enhanced the acute tubular phosphaturic response to PTH (2.5 IU/h i.v.) without affecting the action of the peptide hormone on Ca reabsorption and cyclic-3',5'-AMP excretion. The influence of 1,25(OH)(2)D(3) on the phosphaturic response to PTH could not be ascribed to an increased plasma concentration and(or) filtered load of Pi during the administration of the peptide hormone. However, it could be, at least in part, related to the elevation in the basal level of plasma Pi which was observed in the 1,25(OH)(2)D(3)-treated animals. The results also indicate that 1,25(OH)(2)D(3) significantly enhanced the calcemic response to PTH, which was blunted in these conditions of phosphate deprivation. Unlike 1,25-(OH)(2)D(3), 25-hydroxyvitamin D(3) did not unmask the phosphaturic effect of PTH in phosphate-depleted animals, even when given in doses 100 times larger. Thus, 1,25(OH)(2)D(3) displays a selective and powerful activity in preventing the occurrence of tubular resistance to the phosphaturic action of PTH during Pi depletion. This finding suggests the existence of an important interaction between dietary Pi, 1,25(OH)(2)D(3), and PTH in the homeostasis of phosphate.

Influence of calcium and ionophore 23187 on tubular phosphate reabsorption

In previous studies it has been demonstrated that a decline of plasma calcium concentration accounts for the decrease of phosphate reabsorption in thyroparathyroidectomized (TPTX) rats undergoing phosphate loading. Microinfusion studies were performed in TPTX rats in order to discriminate between a systemic effect of calcium an a direct renal effect. Thyroparathyroidectomized animals were infused with a phosphate solution continuously. When plasma calcium concentration fell below 1.30 mmol/l, proximal convoluted tubules were microinfused with a phosphate tracer solution for 42 min. After 18 min a calcium chloride-containing solution was applied superficially (superfused) to the area of the microinfused tubule. This elevation of peritubular calcium concentration led to an immediate increase of phosphate reabsorption up to 12% of the microinfused phosphate load within 24 min. In another series of experiments, the calcium specific ionophore A23187--a substance which is known to increase intracellular calcium--was superfused on the microinfused tubule. This resulted again in an increase of fractional phosphate reabsorption of about 15% after 24 min. In contrast, when calcium chloride-free as well as ionophore-free solutions were superfused fractional phosphate reabsorption decreased (7%). From these data we conclude that 1. calcium has a direct renal effect on phosphate reabsorption in the absence of parathyroid hormone and 2. intracellular calcium appears to be a major parameter in the regulation of renal phosphate transport under these conditions.

Effect of treatment with parathyroid extract on bone parameters and metabolism of 3H-25-hydroxyvitamin D 3 in Hypocalcemic Thyroparathyroidectomized Rats

Thyroparathyroidectomized (TPTX) rats fed diets containing 0.1% calcium, 0.6% phosphorus (low calcium), or 0.6% calcium, 0.6% phosphorus (normal calcium) become hypocalcemic and hyperphosphatemic. Inhibitory effects of parathyroid extract (PTE; 20 Units/100 g twice daily, 8–9 days) on rates of bone formation, matrix apposition, and osteoid maturation were observed in TPTX rats fed the low calcium diet, but not in those fed the normal calcium diet. Conversion of 25-hydroxyvitamin D 3 to 1,25-dihydroxyvitamin D 3 was increased in response to PTE only in TPTX rats fed the normal calcium diet. In this group increased formation of 1,25-dihydroxyvitamin D 3 was associated with a significant reduction in the width of the mineralizing front. Our results indicate that serum calcium plays an important role in modulating the effect of PTE on metabolic processes in bone and kidney.

Role of calcium in the decline of phosphate reabsorption during phosphate loading in acutely thyroparathyroidectomized rats.

In acutely thyroparathyroidectomized (TPTX) rats infusion of inorganic phosphate leads-after saturation of the reabsorptive system-to a continuous decline of the reabsorptive capacity. The present study is designed to define parameters which are responsible for this phenomenon. Animals are infused a phosphate solution (100 mmol/l, pH 7.4, 0.2 ml/min·kg BW) and a phosphate concentration in plasma of about 5.5 mmol/l is maintained for up to 7 h. While glomerular filtration rate as well as plasma sodium concentration remain virtually constant, plasma potassium concentration initially decreases within the first 4 h of the experiment, but increases again after that period. Phosphate reabsorption declines by some 30%, plasma calcium concentration falls from 1.87±0.03 to 1.11±0.05 mmol/l. The animals develope a mixed respiratory and metabolic alkalosis with a plasma pH of 7.54±0.01, a carbon dioxide tension of 4.66±0.13 kPa (35±1 mm Hg) and a plasma bicarbonate concentration of 28.2±1.3 mmol/l. Phosphaturia leads to osmotic diuresis, to an increase of urine pH and titrable acid. When the elevated plasma pH is normalized phosphate reabsorption continues to decline. When the elevated plasma bicarbonate is lowered no further significant change of phosphate reabsorption is found. When, however, the decreased plasma calcium is restored by infusion of calcium chloride a significant increase of phosphate reabsorption up to control values is demonstrated (P<0.01). From these data we conclude that hypocalcaemia in phosphate loaded TPTX rats is the crucial parameter leading to the decline of renal phosphate reabsorption.

Influence of parathyroid hormone on glomerular ultrafiltration in the rat.

Experiments were performed on 22 plasma-expanded Munich-Wistar rats to investigated the effects of parathyroid hormone (PTH) on the determinants of glomerular ultrafiltration. Mean values for single nephron filtration rate (SNGFR), glomerular plasma flow rate (QA), systemic oncotic pressure, and transglomerular hydraulic pressure difference (deltaP) were similar in acutely thyroparathyroidectomized (TPTX) rats and non-TPTX rats. Nevertheless, the glomerular capillary ultrafiltration coefficient (Kf) was uniformly higher in TPTX rats (greater than 0.113 +/- 0.005 (SE) nl/(s.mmHg)] than in non-TPTX controls (0.088 +/- 0.005). In TPTX rats, infusion of a submaximal dose (1 U/kg per min) of PTH resulted in significant decreases in SNGFR at constant QA and deltaP, due primarily to return of Kf to non-TPTX levels. Infusion of 10 U/kg per min of PTH to non-TPTX rats further reduced Kf, on average to 0.042 +/- 0.001 nl/(s.mmHg), leading to further reduction in SNGFR, whereas QA and deltaP again remained constant. These findings suggest that PTH may play an important role in modulating Kf, and consequently, SNGFR.

889 THE METABOLISM OF LEAD-203 (aoaPb) IN THYROPARATHYROIDECTOMIZED (TPTX) RATS AFTER INFUSIONS WITH CALCIUM (Ca) AND ZINC (Zn)

Previous data in children and animals have shown that dietary deficiencies of Ca and Zn increase the intestinal absorption of Pb thereby increasing Pb toxicity. To define further the interactions of Pb, Ca and Zn, TPTX rats were given IV 7mg/kg of Pb + 25μCi 203Pb and placed in metabolism cages. 4 days later Ca (.232mM) or Zn (.015mM) were infused via a catheterized tail vein for 6H. Measurements were made of stable Pb and 203Pb from aliquots of total organs, urine and blood, once rats were sacrificed from 6-72H after infusion. The results (*= p<.01) were expressed as cpm ratios of Treated (T)/saline-infused Controls (C). The T/C ratios were: Though soft tissue displacement of 203Pb was produced by Ca and Zn, the majority of 203Pb released came from bone with subsequent repletion of soft and hard tissue at 72H. These data indicate that interactions between Pb, Ca and Zn occur at several tissue sites besides the intestine. These complex interactions likely involve metal ion radii, and the activation of Ca- and Zn- sensitive ATPases and alkaline phosphatases, respectively.

887 CALCITONIN (CT) INHIBITS AND PARATHYROID HORMONE (PTH) ENHANCES THE MOBILIZATION OF LEAD-203 (303Pb) IN THYROPARATHYROIDECTOMIZED (TPTX) RATS

Previous results in TPTX rats infused with PTH have shown marked redistribution of 203Pb in hard and soft tissues with a transiently small increase in urinary Pb excretion. Since CaNa EDTA (EDTA) produced rapid depletion of bone 203Pb coincident with a large increase in urinary Pb excretion, this study was undertaken to define further the interactions of EDTA, PTH, and CT on the tissue distribution of 203Pb. Once 25μCi 203Pb were given IV, TPTX rats were placed in metabolism cages; and 4 days later, EDTA, EDTA+PTH, or EDTA+CT were infused by a catheterized tail vein for 6H. Animals were sacrificed at 6 and 48H; and the results were expressed as the cpm Treated (T)/EDTA (E) Ratios, where *= p< .01, different from E: These data indicate that CT inhibits EDTA's actions by blocking removal of 203Pb from bone. PTH, however, markedly enhances the effects of EDTA by increasing depletion of 203Pb from bone primarily, with subsequent redistribution of 203Pb to soft tissues. These dramatic effects of PTH may be of considerable clinical importance in modifying, to an extent, the toxic activities of Pb.

Acute effects of salmon calcitonin on renal electrolyte excretion in intact, thyroparathyroidectomized and sulfacetylthiazole-induced uremic rats.

Acute effects of salmon calcitonin (CT) on renal electrolyte excretion were investigated in intact, thyroparathyroidectomized (TPTX) and uremic rats. Glomerular filtration rate did not change during CT infusion and there was no volume expansion in any experimental group. Plasma calcium levels gradually fell below the control period in each experimental group. Urinary calcium excretion increased at the early period in both intact and TPTX rats but fell below the control period with the continuous infusion of CT. In uremic rats, a decrease in plasma calcium was followed by a decrease in calcium excretion. Plasma phosphate gradually decreased and simultaneously measured phosphate excretion increased in both intact and TPTX rats. In uremic rats, however, there was no change in phosphate excretion and only a slight decrease of plasma phosphate. Phosphaturia is the result of the predominant renal action of CT and occurs even when the filtered load of phosphate decreases. In uremic animals, there appears to be a resistance to exogenous CT which manifests itself by the absence of natriuretic, calciuric and phosphaturic responses.

Regulation of the tubular transport of phosphate in the rat: role of parathyroid hormone and 1,25-dihydroxyvitamin D3.

The reduced capability of the tubular Pi transport to adapt to a high Pi diet in TPTX rats can be normalized by physiological doses of 1,25-(OH)2D3. This suggests that the chronic consequence of a lack of PTH could be due, at least in part, to the reduced production of 1,25-(OH)2D3. The mechanism of Pi adaptation appears to be the most important regulator of Pi excretion in the growing rats, since it can markedly alter the acute phosphaturic response to parathyroid hormone.

Calcium and sodium excretion in rats in response to prolonged treatment with polythiazide.

The hypocalciuric response to prolonged polythiazide (PTZ) administration has been investigated in intact and thyroparathyroidectomized (TPTX) rats. After 3 control days, PTZ was given for 6 days (0.1 mg/100 g body weight . 24 h p.o.). In both groups, calcium excretion fell on day 1 of PTZ and remained depressed thereafter. In the intact rats, this decrease was associated with increased sodium excretion and urine output on treatment day 1. In the TPTX rats, hypocalciuria occurred without change in sodium excretion or body weight; urine output increased on the first 2 days. Thus PTZ can reduce calcium excretion in the absence of parathyroid hormone, changes in sodium excretion, and changes in body weight (an estimate of body fluid balance with constant food intake).

Changes in red cell space of bone in hypocalcemic states: studies in rat femur.

With the use of technetium-99m-labeled red cells, the red cell space of the femur was found to be increased in rats fed a 0.01 percent Ca diet for 4 wk, at which time they were also hypocalcemic. Rats fed the same diet for 2 wk did not demonstrate hypocalcemia nor hypervascularity of the femur. Thyroparathyroidectomized (TPTX) rats fed the calcium-deficient diet produced hypocalcemia nor hypervascularity as did TPTX rats fed a normal diet for 4 wk. However, bone vascularity was normal at 2 wk post-TPTX (normal diet) when the degree of hypocalcemia was less marked. Inhibition of prostaglandin synthetase with oral indomethacin 0.2 mg/100 g per 12 h for 60 h did not alter the red cell space estimates but did increase bone blood flow in both normal and calcium-deficient animals. Acute restoration of normocalcemia with CaCl2 orally in the calcium-deficient rats did not revert the bone hypervascularity. The evidence suggests that in these models of hypocalcemic states, the rise in the vascular space of bone does not result from the influence of PTH, calcitonin, diet, or prostaglandins.

Effect of 1,25-dihydroxyvitamin D3 on the renal handling of Pi in thyroparathyroidectomized rats.

The kidney adapts its tubular capacity to transport inorganic phosphate (P(i)) according to the dietary supply of P(i) in both intact and thyropara-thyroidectomized (TPTX) rats. However, in TPTX rats the capability of the renal tubule to adapt to a high P(i) diet is diminished. In TPTX rats the production of the active vitamin D(3) metabolite, 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], is also reduced. 1,25-(OH)(2)D(3) has been shown to have a marked effect on P(i) metabolism. Therefore the question arises whether the deficient production of 1,25-(OH)(2)D(3) contributes to the alteration of the tubular transport of P(i) observed in chronically TPTX rats. In the present investigation, vitamin D-replete rats were sham operated (SHAM) or thyroparathyroidectomized and then pair fed diets containing either 0.2 or 1.2 g/100 g P for 7 days. During this period, groups of SHAM and TPTX rats received i.p. 2 x 13 pmol/day of 1,25-(OH)(2)D(3), a dose which was shown to just normalize the decreased intestinal absorption of Ca and P(i) in TPTX rats. The capacity of tubular P(i) transport was then assessed by measuring the fractional excretion of P(i) (FEP(i)) at increasing plasma P(i) concentration ([P(i)](Pl)) obtained by acute infusion of P(i). The results show that in SHAM rats fed either P diet, 1,25-(OH)(2)D(3) has no effect on the renal handling of P(i). In TPTX rats fed 1.2 g/100 g P diet, 1,25-(OH)(2)D(3) increases FEP(i) over a wide range of [P(i)](Pl.) In TPTX rats fed a 0.2 g/100 g P diet, 1,25-(OH)(2)D(3) does not alter FEP(i) up to a [P(i)](Pl) of 3.0-3.5 mM, but does increase it at higher [P(i)](Pl.) In fact, on both diets TPTX rats supplemented with 1,25-(OH)(2)D(3) appear to have the same renal handling of P(i) as SHAM counterparts. The effect of 1,25-(OH)(2)D(3) was not associated with a change in urine pH or in urinary excretion of cyclic AMP and was maintained under marked extracellular volume expansion. It was associated with a rise in plasma calcium in the TPTX rats fed the high, but not the low, P diet. In TPTX rats fed 1.2 g/100 g P diet, 25-hydroxyvitamin D(3) in doses of 2 x 130 or 2 x 1,300 pmol/day i.p. did not increase FEP(i.)In conclusion, 1,25-(OH)(2)D(3) administered in physiological amounts to TPTX rats restores to normal the capability of the renal tubule to excrete P(i) and to adapt to large variation in dietary P(i). The results suggest that 1,25-(OH)(2)D(3) plays an important role in the regulation of the renal handling of P(i) and that the chronic change in the tubular capacity to transport P(i) after TPTX may be due to the decreased formation of 1,25-(OH)(2)D(3).

Effect of endogenous and infused parathyroid hormone on plasma concentrations of recently administered 45Ca.

The net rate of loss of45Ca from plasma was monitored in normal, thyroparathyroidectomized (TPTX), and nephrectomized rats. Also studied was the effect of a 24 h intravenous infusion of PTH in TPTX rats. The45Ca was injected after an overnight fast and 1 to 4 h prior to the time the first blood sample was obtained.

Relationship between phosphaluria and acute hypercapnia in the rat.

Standard clearance studies were performed in mechanically ventilated intact and acutely thyroparathyroidectomized (TPTX) rats to document and characterize the effect of hypercapnia (HC) on urinary phosphorus excretion (U(P)V). HC as compared to normocapnia (NC) was associated with an increase in U(P)V in intact (62.5 vs. 7.93 mug/min) and TPTX (30.5 vs. 0.59 mug/min) rats, an increase in filtered load of phosphorus in intact (218 vs. 191 mug/min) and TPTX (243 vs. 146 mug/min) rats, an increase in blood bicarbonate concentration in intact (27.8 vs. 26.0 meq/liter) and TPTX (24.5 vs. 22.3 meq/liter) animals, and a decrease in blood pH in intact (7.15 vs. 7.42) and TPTX (7.07 vs. 7.39) rats. Additional TPTX rats with NC and HC were studied during phosphorus infusion at a comparable filtered load of phosphorus (NC = 307 mug/min and HC = 328 mug/min). U(P)V was 18.5 mug/min in NC and 85.2 mug/min in HC animals. Intact NC animals infused with NaHCO(3) achieved a blood bicarbonate of 45.9 meq/liter compared to 26.0 meq/liter in intact NC NaCl-infused rats. U(P)V was 10.0 mug/min in the NaHCO(3) and 7.93 mug/min in NaCl-infused animals. In intact HC animals infused with NaHCO(3), blood pH was 7.36 compared to 7.42 in NC intact NaCl-infused animals. U(P)V was 83.2 mug/min in the HC bicarbonate-infused and 7.93 mug/min in the NC NaCl-infused rats. These experiments demonstrate that elevated blood carbon dioxide tension per se increases U(P)V. Increases in filtered load of phosphorus and blood bicarbonate which are associated with HC contribute to the phosphaturia as does parathyroid hormone. The phosphaturia is not dependent upon reduction of extracellular pH.

Effect of thyroparathyroidectomy of calcium metabolism in rats: role of 1,25-dihydroxyvitamin D3.

Thyroparathyroidectomy (TPTX) decreases plasma calcium, bone formation and resorption, and tubular reabsorption of calcium. It also reduces the production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] which very likely results in the decrease in the intestinal calcium absorption (Vna) observed after TPTX. We have examined whether the influence of TPTX on plasma calcium and bone calcium fluxes could be corrected by doses of 1,25-(OH)2D3 (2 X 13 pmol/day ip), which just normalize Vna. The study was made by calcium balance and 45Ca kinetics in rats receiving a normal supply of vitamin D3. The results show that in TPTX rats physiological doses of 1,25-(OH)2D3 increased plasma calcium and decreased plasma phosphate. Calcium retention was not fully corrected because 1,25-(OH)2D3 increased urinary calcium excretion. The deposition into and the release of calcium from bone were enhanced by 1,25-(OH)2D3 but remained lower than in pair-fed sham-operated animals. Thus, in as much as the diminished renal production of 1,25-(OH)2D3 in TPTX is entirely responsible for the reduced Vna, the decrease in 1,25-(OH)2D3 could only partly explain the effect of thyroparathyroidectomy on bone calcium fluxes.