Effects of human calcitonin on water and electrolyte movements in rat juxtamedullary nephrons: inhibition of medullary K recycling

The effects of synthetic human calcitonin (HCT) on water and electrolyte deliveries to the thin limbs of Henle's loop of juxtamedullary nephrons were investigated by micropuncture in the rat. To avoid undesirable interference with exogenous calcitonin, experiments were performed in hormone-deprived rats with reduced circulating calcitonin, antidiuretic hormone, parathyroid hormone and glucagon, all four of which stimulate the adenylate-cyclase activity in the thick ascending limb and the distal tubule. Administration of HCT (1.0 mU/min·100 g body wt) to such rats significantly reduced the urinary fractional excretion rate of water, Mg, Ca and K. At the tip of the long-looped nephrons, the fractional delivery of water diminished in the presence of HCT, although the glomerular filtration rate of these nephrons was unaltered. Simultaneously, the loop fluid osmolality rose significantly. HCT, however, did not alter the fraction of total filtered solutes remaining in the thin limbs, nor the NaCl fractional delivery. As previously observed in this laboratory with dDAVP, the reduced fractional delivery of water at the hairpin turn was accompanied by a decrease in Mg and Ca deliveries in rats given HCT, indicating that the handling of these two ions along the descending limb may be linked in part to the water movements in this nephron segment. The fractional deliveries of K at the hairpin turn and in urine were significantly correlated, and both decreased in the presence of HCT. Since, as shown previously, HCT reduces the net addition of K along the superfical distal tubule, it is concluded that calcitonin inhibits the medullary recycling of K between the nephron terminal segments and the loop of Henle of juxtamedullary nephrons.     

Stimulation by human calcitonin of electrolyte transport in distal tubules of rat kidney

The effects of human calcitonin (HCT) on the distal tubule were investigated by micropuncture in hormone-deprived rats, i.e. in the absence of parathyroid hormone, antidiuretic hormone and glucagon, which might have masked these effects. Two groups of rats were studied: hormone-deprived and hormone-deprived+HCT, infused at 1.0 mU/min\100 g b.w. In the urine, HCT markedly reduced Ca and Mg excretion whereas excretion of water, Na and K was not significantly affected. Along the distal tubule, HCT strongly enhanced Na, Cl, Mg, Ca and total solute reabsorption, decreased K secretion but did not alter water or phosphate transport. It is concluded that HCT stimulated Na, Cl, Ca and Mg reabsorption. If, as suggested, HCT also stimulated the reabsorptive component of K transport, the hormone should therefore elicit the same physiological effects in the distal tubule and the thick ascending limb.     

Stimulation by glucagon and PTH of Ca and Mg reabsorption in the superficial distal tubule of the rat kidney

The effects of glucagon and PTH on electrolyte reabsorption in the distal tubule were investigated in rats deprived of vasopressin, calcitonin, PTH, and glucagon. Micropunctures of distal tubule, at a late and an early site of a same nephron, have been performed in 23 rats, nine control, seven infused with glucagon (5 ng·min^–1·100 g^–1 b.w.) and seven with PTH (5 mU·min^–1·100 g^–1 b.w.). The Ca and Mg reabsorptive capacity of the distal segment was increased by glucagon and by PTH. Moreover, fractional Na and Cl reabsorption was significantly higher than in control during PTH administration. A K secretion appeared during the administration of both hormones. No phosphate net transport was observed in any group. Finally, the data presented here, together with those previously reported, indicate that the increase of Ca and Mg renal reabsorption observed with glucagon and PTH results from an effect located in both Henle's loop, where the bulk of Ca and Mg is reabsorbed, and the distal tubule.     

Glucagon inhibits water and NaCl transports in the proximal convoluted tubule of the rat kidney

The effects of glucagon on water and electrolyte transport in the kidney were investigated on hormone-deprived rats, i.e. thyroparathyroidectomized diabetes insipidus Brattleboro rats infused with somatostatin. Glucagon consistently inhibited the reabsorption of water and Na⁺, Cl^–, K⁺ and Ca²⁺ along the proximal tubule accessible to micropuncture, leaving the reabsorption of inorganic phosphate (P_i) untouched. In the loop, besides its previously described stimulatory effects on Na⁺, Cl^–, K⁺, Ca²⁺ and Mg²⁺ reabsorption, glucagon strongly inhibited P_i reabsorption, very probably in the proximal straight tubule. These effects resulted in a significant phosphaturia and considerable reductions of Mg²⁺ and Ca²⁺ excretions. The effects of glucagon at both the whole kidney and the nephron levels are very similar to those previously described for calcitonin. In the absence of an adenylate cyclase system sensitive to glucagon and calcitonin in the rat proximal tubule, and from the analogy of their physiological effects with those elicited by parathyroid hormone, it is suggested that glucagon and calcitonin exert their inhibitory effects on Na and P_i reabsorption in the proximal tubule through another pathway, which could be the phosphoinositide regulatory cascade.     

Stimulation of tubular reabsorption of magnesium and calcium by antidiuretic hormone in conscious rats

The effect of antidiuretic hormone on urinary electrolyte excretion was investigated by clearance techniques in conscious rats in metabolic cages. Brattleboro rats with hereditary diabetes insipidus (DI) (no ADH) were studied in the absence of exogenous ADH (control group = C,n=4), and after several weeks of continuous dDAVP infusion (period A) followed by discontinuation of dDAVP (period B) (experimental group = E,n=6). dDAVP, a non-pressor antidiuretic analogue to ADH, induced 1) a high urine concentration (2,645±44 (SEM) in group E vs 131±6 mosmol/kg H₂O in group C),P<0.001; 2) no significant change in plasma osmolality (288±2 vs 297±7 mosmol/kg H₂O respectively) and in plasma concentration of major electrolytes, Na, K, Cl, Mg, and Ca; 3) a large decrease in urinary excretion of calcium and magnesium and no change in other electrolyte or total osmolar excretion. Fractional excretions in rats of groups C and E during period A were, respectively, for Na: 0.59±0.03 (SEM) and 0.51±0.33% (NS), for Ca: 2.92±0.62 and 0.34±0.05% (P<0.001) and for Mg: 7.75±0.83 and 1.38±0.28% (P<0.001). After treatment discontinuation, plasma osmolality in group E rose to 304±2 mosmol/kg H₂O (P<0.01 compared to period A) with slight increases in plasma Na and Cl concentrations. Urine osmolality fell below, and urine flow rate rose above values observed in the control group. Fractional excretion of Ca and Mg rose to values seen in DI rats (3.30±0.37%, NS, for Ca) or above (26.95±0.65%,P<0.001, for Mg), with no change in other solute fractional excretion. Other works, from our and other's groups have shown that 1) long-term exposure to dDAVP induces a marked hypertrophy of the epithelium of the thick ascending limb of Henle's loop in its medullary part (MTAL) and 2) dDAVP induces an increase in Ca and Mg tubular reabsorption between end proximal and early distal sites of micropuncture. Taken together, these results suggest that the effects of ADH on divalent cation fractional excretion, seen in the present study, probably results from an increased Ca and Mg voltage-dependent reabsorption in the MTAL. This reabsorption is linked to the increased salt transport induced in this segment, both by a direct effect of ADH and by an indirect effect resulting from the increased solute delivery to the MTAL in the concentrating kidney.     

Micropuncture study on the effects of lithium on proximal and distal tubule function in the rat kiney

Micropuncture studies were performed in rats infused with LiCl to induce stable plasma lithium concentrations of 2–3 mEq/l, or with an equivalent amount of NaCl. In free flow experiments LiCl reduced proximal tubule fractional reabsorption of sodium and potassium. Reduced reabsorption of bicarbonate, as reflected by a decrease in TF/P_cl, was also observed. Proximal fractional reabsorption of chloride, however, was not affected. The TF/P_In at the end proximal tubule was 2.6±0.2 (mean ±SEM) in controls and 2.1±0.1 in experimental animals (P<0.025). In the distal portions of the nephron lithium treatment caused a fall in fractional reabsorption of water and sodium, while potassium secretion was stimulated in the distal tubule.Previous studies have indicated that lithium influences antidiuretic hormone stimulated water transport in the collecting duct. These experiments demonstrate that lithium also affects the transport of water and electrolytes in multiple nephron segments, including the proximal and distal convolution.     

Magnesium transport in the renal distal convoluted tubule

The distal tubule reabsorbs approximately 10% of the filtered Mg(2+), but this is 70-80% of that delivered from the loop of Henle. Because there is little Mg(2+) reabsorption beyond the distal tubule, this segment plays an important role in determining the final urinary excretion. The distal convoluted segment (DCT) is characterized by a negative luminal voltage and high intercellular resistance so that Mg(2+) reabsorption is transcellular and active. This review discusses recent evidence for selective and sensitive control of Mg(2+) transport in the DCT and emphasizes the importance of this control in normal and abnormal renal Mg(2+) conservation. Normally, Mg(2+) absorption is load dependent in the distal tubule, whether delivery is altered by increasing luminal Mg(2+) concentration or increasing the flow rate into the DCT. With the use of microfluorescent studies with an established mouse distal convoluted tubule (MDCT) cell line, it was shown that Mg(2+) uptake was concentration and voltage dependent. Peptide hormones such as parathyroid hormone, calcitonin, glucagon, and arginine vasopressin enhance Mg(2+) absorption in the distal tubule and stimulate Mg(2+) uptake into MDCT cells. Prostaglandin E(2) and isoproterenol increase Mg(2+) entry into MDCT cells. The current evidence indicates that cAMP-dependent protein kinase A, phospholipase C, and protein kinase C signaling pathways are involved in these responses. Steroid hormones have significant effects on distal Mg(2+) transport. Aldosterone does not alter basal Mg(2+) uptake but potentiates hormone-stimulated Mg(2+) entry in MDCT cells by increasing hormone-mediated cAMP formation. 1,25-Dihydroxyvitamin D(3), on the other hand, stimulates basal Mg(2+) uptake. Elevation of plasma Mg(2+) or Ca(2+) inhibits hormone-stimulated cAMP accumulation and Mg(2+) uptake in MDCT cells through activation of extracellular Ca(2+)/Mg(2+)-sensing mechanisms. Mg(2+) restriction selectively increases Mg(2+) uptake with no effect on Ca(2+) absorption. This intrinsic cellular adaptation provides the sensitive and selective control of distal Mg(2+) transport. The distally acting diuretics amiloride and chlorothiazide stimulate Mg(2+) uptake in MDCT cells acting through changes in membrane voltage. A number of familial and acquired disorders have been described that emphasize the diversity of cellular controls affecting renal Mg(2+) balance. Although it is clear that many influences affect Mg(2+) transport within the DCT, the transport processes have not been identified.     

Calcium transport across segments of the rabbit distal nephron in vitro.

The mechanism of Ca2+ transport by various segments of the distal nephron was studied in vitro using the isolated perfused tubule technique. Calcium absorption in the distal convoluted tubule (DCT) and the granular portion of the cortical collecting duct (CCTg) was significantly enhanced in the presence of parathyroid hormone (PTH), 3 X 10(-2) U/ml. Na+ was absorbed from and K+ was secreted into the lumen of the DCT. The presence of amiloride (5 X 10(-5) M) or furosemide (5 X 10(-5) M) in the perfusate of DCT each caused a partial inhibition of Na+ but not Ca2+ absorption. The foregoing result with Na+ is consistent with the heterogeneous nature of DCT. Net Na+ absorption and K+ secretion also occurred in the CCTg; both processes were completely inhibited by amiloride. Ca2+ absorption occurred in the thick ascending limb of Henle's loop; it was not enhanced by PTH, and the results were consistent with passive movement. No net Ca2+ movement was observed in the nongranular (light) segment of the cortical collecting tubule in the presence or absence of PTH or dibutyryl cyclic adenosine monophosphate.     

Effects of parathyroid hormone on electrolyte transport in the hamster nephron.

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.     

Glucagon receptors along the nephron: [125I]glucagon binding in rat tubules

Binding of [¹²⁵I]glucagon was measured in microdissected pieces of tubules from the rat nephron. Specific glucagon binding sites were found only in nephron segments containing a glucagon-sensititive adenylate cyclase activity. At 7.5 nM labelled hormone, higher levels of specific binding (16–27×10^–18 mol mm^–1) were found in the thick ascending limb of the Henle's loop and in the distal convoluted tubule and lower binding levels (2–5×10^–18 mol mm^–) in the collecting tubule whereas specific binding could not be detected in the proximal tubule and in the thin segments of the Henle's loop. In the medullary thick ascending limb, Scatchard analysis of specific [¹²⁵I]glucagon binding indicated an apparent equilibrium dissociation constant of 2.4 nM. The stereospecificity of binding sites in medullary thick ascending limbs and medullary collecting tubules, was assessed by competition experiments using unlabelled glucagon, enteroglucagon and unrelated hormones (vasopressin, calcitonin, parathyroid hormone and insulin); in both segments, glucagon was more active than enteroglucagon in displacing labelled glucagon from its tubular binding sites, whereas all other hormones tested were inactive. These results indicate that tubule binding sites might be the physiological receptors for glucagon involved in adenylate cyclase activation.Abbreviations PCT proximal convoluted tubule - TDL thin descending limb - TAL thin ascending limb - MAL medullary thick ascending limb - CAL cortical ascending limb - DCT distal convoluted tubule - CCT cortical collecting tubule - MCT medullary collecting tubule     

Calcium transport in the nephron.

Ionized and complexed calcium are filtered at the glomerulus and more than 95% of the filtered load is reabsorbed along the length of the nephron. In the proximal convoluted tubule calcium is absorbed in proportion to sodium and water, suggesting a passive mechanism. The high permeability of this segment is compatible with passive transport, but evidence for active transport has been advanced. A role for Ca2+-ATPase and/or for a Ca2+/Na+ antiport has also been proposed. The straight portion of the proximal tubule appears to transport calcium actively but little is known about the mechanism and regulation of calcium absorption in this segment. Both passive and active transport of calcium in the thick ascending limb have been demonstrated, and heterogeneity in the function of medullary and cortical segments has been proposed. Definite evidence has been advanced for avid active calcium absorption in the distal convoluted tubule. Both chlorothiazide and parathyroid hormone enhance the transport of calcium in this segment. The granular portion of the collecting tubule resembles in its properties and function the distal convoluted tubule. The light portion, however, is incapable of transporting calcium. The distal tubule and collecting tubule may be the final regulators of urinary excretion of calcium but much more data are required before this view can be adopted.     

Distal site of action of parathyroid hormone on phosphate reabsorption.

The sites of inhibited phosphate transport following administration of bovine parathyroid hormone (bPTH) to thyroparathyroidectomized (TPTX) dogs were investigated. Phosphate reabsorption by the proximal and distal nephron was studied using recollection micropuncture, stop-flow methodology, and electron-probe microanalysis. Following bPTH, delivery of phosphate from the proximal tubule increased from 26 to 37% of the filtered load, P less than .01. Fractional phosphate excretion increased from 2.3 +/- 1.5 to 21.4 +/- 2.3%, P less than .001. The increased delivery of phosphate at the point of micropuncture in the proximal tubule accounted for approximately half of the phosphaturia. In six TPTX dogs, which were saline loaded, similiar increases in phosphate delivery from the proximal tubule from 27 +/- 1 to 36 +/- 2% of the filtered load resulted in a strikingly smaller phosphaturia, 5.1 +/- 1 to 9.8 +/- 2.4%, NS. In stop-flow experiments, phosphate concentratin ratios were slightly increased in the proximal nephron and markedly increased in the distal nephron following bPTH. It is concluded that parathyroid hormone markedly decreases phosphate transport in the distal nephron.     

Antidiuretic hormone restores the endolymphatic longitudinal K+ gradient in the Brattleboro rat cochlea

In the cochlea, endolymph is hyperosmotic to plasma and perilymph. To test the hypothesis that antidiuretic hormone is involved in the modulation of endolymph secretion, the electrochemical composition of cochlear fluids, endolymph and perilymph, was studied in three groups of anaesthetized rats: control Long Evans rats, homozygous Brattleboro rats that are genetically deprived of antidiuretic hormone, and Brattleboro rats that were treated with antidiuretic hormone (dDAVP, 0.5 g/100 g body weight/24 h during 8 days). Endolymph was sampled from the scala media at each turn of the cochlea and perilymph from the scala vestibuli. In Long Evans rats, the endocochlear potential, the endolymphatic K⁺ and Cl^– concentrations decreased from base to apex of the cochlea as previously reported in guinea pigs and Sprague Dawley rats. In Brattleboro rats, the endocochlear potential and the Cl^– concentration gradients were still present, whereas the K⁺ con centration gradient was absent. This K⁺ gradient was restored by the administration of dDAVP, which increased the K⁺ concentration at the base of the cochlea. This work indicates that the K⁺ secretion in endolymph, and thus the osmolality, may be locally modulated by the antidiuretic hormone, probably via V₂ receptors.     

Effects of parathyroid hormone on renal tubular calcium and phosphate handling

Central to the maintenance of calcium homeostasis is the regulated reabsorption of calcium along the nephron. To this end, parathyroid hormone (PTH) is released from the parathyroid gland in response to lowered plasma calcium levels. This hormone acts through the PTH 1 receptor along the nephron to increase urinary phosphate excretion and decrease urinary calcium excretion. In the proximal tubule, PTH inhibits phosphate reabsorption by reducing the abundance of sodium phosphate cotransporters in the apical membrane. PTH likely decreases calcium reabsorption from the proximal tubule, by reducing the reabsorption of sodium, an event necessary for the paracellular movement of calcium across this segment. In the thick ascending limb (TAL), PTH increases calcium permeability and may increase the electrical driving force thereby increasing calcium reabsorption in the TAL. Finally, in the distal convolution, PTH acts to increase transcellular calcium reabsorption by increasing the activity and abundance of the apically expressed calcium channel TRPV5.     

Micropuncture study of water and electrolyte movements along the loop of henle in Psammomys with special reference to magnesium,calcium and phosphorus

Summary Cortical and papillary micropuncture experiments were carried out on Psammomys undergoing mild hypertonic salt diuresis. Tubular fluid was collected along the proximal tubule or at the early distal tubule level, and at the tip of the longest Henle loop.³H-inulin, Na, K, Cl, Mg, Ca and P concentrations, as well as osmotic pressure, were determined in all samples. The results indicate a) no large net water movement along the loop; b) substantial addition of Na, K, Cl, Mg, and to a lesser extent Ca, along the descending limb, in proportion to the gradient; c) the tubular flow rate of phosphorus remains constant at the tip of the loop irrespective of the gradient. The constancy of the load of Na, K, Cl, Mg and Ca delivered to the distal superficial nephron, irrespective of the urinary osmotic pressure, indicates that medullary recycling between the ascending and descending limbs exists for Mg, Cl, and Ca, and confirms its existence for Na and K. In contrast, phosphorus behaves like inulin along the descending limb. A general conclusion is that in Psammomys the concentrating process along the descending limb of Henle results mainly from net addition of solutes, and not from water withdrawal.Part of this work was presented at the 5th Congress of Nephrology, Mexico 1972.     

Inhibitory effect of epinephrine on renal potassium secretion: a micropuncture study

The effect of epinephrine on renal potassium excretion was examined in the rat. In group I KCl was infused acutely to increase plasma K (PK) by 2.0 meq/liter; urinary K excretion (UKV) rose by 1.22 mueq/min. In group II rats, which received a similar dose of KCl but with epinephrine, the increase in PK (delta = 0.8 meq/liter, P less than 0.001) was blunted and UKV was reduced (delta = 0.23 mueq/min, P less than 0.001). To determine whether the reduction in UKV resulted from the smaller increase in PK or from a direct action of epinephrine on renal K transport, a third group of animals received a lower dose of KCl. Despite similar PK levels, the epinephrine group excreted significantly less K in the urine (0.61 vs. 0.93 mueq/min). In group IV propranolol was infused with KCl; UKV was modestly increased. The effects of epinephrine on UKV were unrelated to changes in glomerular filtration rate, urine flow, or UNaV. Micropuncture results showed that at comparable PK levels epinephrine had no direct effect on K secretion by the distal tubule but indirectly inhibited K secretion in this nephron segment by reducing PK. In addition, epinephrine reduced K addition at tubular sites beyond the late distal tubule, most likely in the collecting tubule.     

Distal site of calcium reabsorption in the rat nephron

The sites of outflux of⁴⁵Ca along the nephron were investigated using microinfusion technique in acutely thyroparathyroidectomized (TPTX), intact and TPTX Wistar rats substituted with parathyroid hormone (PTH). In all three groups⁴⁵Ca outflux occurred along the proximal tubule, the loop of Henle and along the distal tubule. After microinfusion into late distal tubules⁴⁵Ca recovery in ipsilateral urine was essentially complete for the TPTX group but was only 83 and 65% for the intact and the PTH substituted animals. Increases in microinfusion flow rate from 2–20 nl/min into early and middle distal tubules resulted in increased urinary recovery of⁴⁵Ca for all three groups. Similarily, increases in microinfusate Ca concentration from 0.2–2.0 and 5.0 mmol/l resulted in increased fractional urinary recovery of⁴⁵Ca both in the presence and absence of PTH. When⁴⁵Ca and³H inulin containing solutions were continuously microinfused into early distal tubules for one hour periods an anticalciuric effect of PTH could be demonstrated. It is concluded that Ca, in addition to its outflux in the proximal tubule and in the loop of Henle, is reabsorbed in the distal tubule accessible to micropuncture. PTH acts anticalciuric at this latter site.     

Effects of hyperoncotic albumin and parathyroid hormone infusion on jejunal electrolyte and water absorption in the rat

Preferential plasma volume expansion by infusion of hyperoncotic albumin solution dialyzed against distilled water (calcium-poor albumin) decreases sodium reabsorption in the dog proximal renal tubule during hydropenia. No such decrease is observed when infusing a calcium-rich hyperoncotic albumin solution. A possible role of parathyroid hormone (PTH) has been postulated. To investigate whether similar changes could be observed in intestinal electrolyte and water absorption, the effects of systemic hyperoncotic albumin infusion on jejunal transport of water, sodium, and calcium were studied in hydropenic rats by perfusing proximal jejunum in situ. It was further sought whether PTH could play a direct role in jejunal electrolyte and water transfer.Following infusion of calcium-poor, sodium-poor hyperoncotic albumin solution (group I), net jejunal absorption of water, sodium, and calcium decreased significantly when compared to control. Concurrently, lumen-to-mucosa (1-m) calcium flux, measured using 45 Ca, diminished significantly. Following infusion of calcium-rich, sodium-poor hyperoncotic albumin solution (group II), no changes in net or unidirectional fluxes were observed. After infusion of calcium-rich, sodium-rich hyperoncotic albumin solution (group III), net jejunal absorption of water and sodium, but not of calcium, were found significantly decreased when compared to control.Plasma ionized calcium increased 10 min after calcium-rich hyperoncotic albumin loading, but decreased significantly at that time when the calcium-poor hyperoncotic albumin solution was infused. However, 30 min after each of the calcium-rich and calcium-poor albumin infusion, plasma ionized calcium was increased in both groups of rats. Plasma immunoreactive PTH was unchanged 30 min after expansion with the calcium-rich solution but it increased significantly after expansion with the calcium-poor solution.Intravenous infusion of bovine PTH (group IV) resulted in a decrease of net jejunal water, sodium, and calcium flux. The decrease in net calcium transport was accompanied by a decrease in 1-m calcium flux. No such changes were observed when PTH was replaced by vehicle (group V).It is concluded that: (1) hyperoncotic albumin infusion induces jejunal water, sodium, and calcium flux changes dependent on the calcium and sodium content of the infused solution: calcium-poor, sodium-poor hyperoncotic albumin infusion leads to a decrease in net jejunal electrolyte and water absorption possibly via stimulation of PTH secretion; (2) sodium-poor hyperoncotic albumin infusion does not modify per se these fluxes in the hydropenic rat; (3) exogenous PTH infusion as well as endogenous stimulation of PTH secretion results in a comparable decrease of jejunal water, sodium, and calcium absorption.     

Effect of calcitonin on urine concentration in the rat

Because mammalian distal nephron segments with both calcitonin- and antidiuretic hormone- (ADH) sensitive adenylate cyclase activity have been described, in vivo and in vitro experiments were performed to study the effect of calcitonin on rat distal nephron water permeability. Calcitonin 1 and 0.1 U/ml, but not 0.01 U/ml, significantly increased the diffusional water permeability in the isolated papillary collecting duct by 15 and 11%, respectively. However, this effect was small when compared with a 68% increase with a supramaximal concentration of ADH (from 4.0 +/- 0.3 to 6.7 +/- 0.9 microns/s; n = 6, P less than 0.01). The normal increase in water permeability with increasing concentration of ADH (0.02 and 0.2 mU/ml) was depressed by the previous addition of calcitonin (1 U/ml) to the bath but was unaltered with the supramaximal ADH concentration (2 mU/ml). Verapamil, a compound that antagonizes cellular calcium entry, did not alter the effect of calcitonin on diffusional water permeability. Calcitonin in concentrations of 0.05, 0.5, and 5 U/ml produced a significant reduction in urine flow and free water clearance. Pretreatment with calcitonin in these concentrations inhibited the antidiuretic action of ADH. These studies suggest that calcitonin acts as a partial agonist to ADH within the distal nephron. It is unclear whether such an action represents a physiological or a pharmacological effect.     

The effect of antidiuretic hormone on the distribution of nephron filtration rates in rats with hereditary diabetes insipidus

Summary The effect of antidiuretic hormone on the distribution of nephron filtration rates was studied in rats with hereditary diabetes insipidus using the Hanssen method for determination of nephron filtration rates as modified by de Rouffignacet al. [18]. Conversion of water diuresis to antidiuresis by infusion of ADH resulted in a moderate, but highly significant increase in the filtration rate of the juxtamedullary nephrons, while the nephrons of all other cortex regions filtered at an unaltered rate. A mechanism based on the action of ADH on distal nephron water permeability is proposed as an explanation: water inflow into the medulla very likely decreases when water diuresis is converted to antidiuresis. This occasions a rise in medullary osmolality which then causes an increase in the apparent viscosity of the blood flowing through the vasa recta. This is responsible for a rise in juxtamedullary postglomerular resistance which results in an increase in the effective filtration pressure and thus in the juxtamedullary nephron filtration rate. The results suggest that an increased juxtamedullary filtration rate participates in the establishment and maintenance of the inner medullary solute gradients, possibly as a consequence of an increased solute delivery to the ascending limbs of the long loops of Henle.This work was supported by the Deutsche Forschungsgemeinschaft.On leave from the University of Melbourne as a recipient of a scholarship from the Deutscher Akademischer Austauschdienst.