Medullary Recycling Research Articles

Type 2 Pseudohypoaldosteronism: New Insights Into Renal Potassium, Sodium, and Chloride Handling

Type 2 Pseudohypoaldosteronism: New Insights Into Renal Potassium, Sodium, and Chloride Handling

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 X 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 longlooped 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 superficial 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.

Effects of dDAVP on rat juxtamedullary nephrons: stimulation of medullary K recycling.

The effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on the handling of water and electrolytes by the juxtamedullary nephrons were studied on rats with reduced circulating levels of antidiuretic hormone (ADH), parathyroid hormone, calcitonin, and glucagon, all of which stimulate the adenylate cyclase system of the thick ascending limb and the distal tubule. In such hormone-deprived rats and in hormone-deprived + dDAVP rats, the concentration of Na, Cl, and total solutes was lower in the ascending than in the descending limbs, whereas the inulin concentration was similar at both sites. dDAVP did not alter the fraction of NaCl remaining in the thin limbs, but tended to reduce that of Mg and Ca. On the other hand, dDAVP significantly increased the fraction of filtered K remaining from 65.8 +/- 5.2 to 107.3 +/- 15.8%. A direct correlation was observed between the fraction of filtered K remaining at the tip of the juxtamedullary loops and the fractional excretion rate of K in urine. Since dDAVP enhances distal K net secretion, as previously shown in our laboratory, these results indicate that the medullary recycling of K from nephron terminal segments to Henle's loop of juxtamedullary nephrons is stimulated by this peptide.

Effects of aldosterone on potassium recycling in the kidney of adrenalectomized rats.

Recent studies have suggested that potassium, like urea, undergoes medullary recycling. The present cortical and papillary micropuncture studies were designed to confirm the existence of medullary potassium recycling and to determine whether acute infusions of aldosterone affected this phenomenon. Thus, nephron segmental analysis of potassium and sodium transport was conducted in adrenalectomized Munich-Wistar rats and similarly prepared rats that received aldosterone acutely to achieve physiological blood levels. The clearance results demonstrated that aldosterone has an acute antinatriuretic and a kaliuretic effect, whereas the micropuncture studies demonstrated that 1) aldosterone increases potassium secretion between early and late distal tubule punctures; 2) aldosterone causes an increase in delivery of potassium to the papillary collecting duct; 3) aldosterone does not increase potassium secretion across the papillary collecting duct; and 4) aldosterone significantly increases medullary potassium recycling as evidenced by increased quantities of potassium present at the bend of the loop of Henle in response to aldosterone infusions. Thus, the studies confirm the existence of potassium recycling and suggest that this phenomenon is a feedback system that, in part, regulates urinary potassium excretion.

Potassium recycling in the renal medulla: Effects of acute potassium chloride administration to rats fed a potassium-free diet

According to the hypothesis of potassium recycling in the renal medulla, a portion of potassium in fluid in the medullary collecting duct is reabsorbed, trapped in the medullary interstitium by countercurrent exchange, and secreted in either the pars recta or descending limb of the juxtamedullary nephron. To examine the effects of an acute change in potassium balance on recycling, we performed a micropuncture study on the exposed papilla of 8 chloride. A second group of 6 rats was studied under identical conditions and infused with potassium chloride and amiloride. In the first group, the fraction of filtered potassium remaining at the end of the juxtamedullary descending limb increased with time to values over 100% concomitantly with the rise in urinary excretion of potassium. A strong association was found between those two variables (P less than 0.025). In the second group, in which the increase in urinary fractional excretion of potassium was prevented by amiloride, the rise in fractional of filtered potassium remaining at the end of the juxtamedullary nephron was abolished. These findings are interpreted as providing further support for the hypothesis of medullary recycling of potassium.

Renal function and concentrating ability in a desert rodent: the gundi (Ctenodactylus vali).

Clearance and cortical micropuncture experiments were carried out on non diuretic gundis. In this species, the kidney has a long and well developed papilla but, unlike other desert rodents, the vascular organization of the outer medulla is very simple. After withdrawal of water supply for either 24 h or 3 days before the experiments, the urine osmolality was only 1,361 +/- 57, n = 9, before and 1,136 +/- 89 mosmol . kg-1 during anesthesia. The GFR per 100 g B.W.(0.450 ml . min-1) is lower than in the rat studied under similar conditions. With regard to electrolytes the tubular handling of Na, Ca, K and Mg is similar to that observed for another desert rodent, psammomys obesus. For P, massive reabsorption (more than 30% of the filtered load) takes place along the distal convoluted tubule. The relatively poor concentrating ability of the gundi's kidney is not due to a lack of medullary recycling of urea since a net addition of urea to short loops of Henle is observed in this species. Physiological and morphological observations concerning the gundi and other desert rodent species suggest that the vascular bundle development in the outer medulla might affect the renal response to water deprivation.

Suppression of potassium-recycling in the renal medulla by short-term potassium deprivation

Recently we proposed that potassium, like urea, normally undergoes medullary recycling from collecting tubule to the pars recta or descending limb of the juxtamedullary nephron and suggested that the extent of recycling is a function of the concentration of potassium in collecting tubule fluid. To test this hypothesis further, we fed young rats a potassium-free diet for 3 days and then prepared them for micropuncture of the left renal papilla. Compared to findings in normally fed animals, potassium deprivation caused a significant fall in plasma potassium and urinary excretion of potassium. There was a striking decrease in the fraction of filtered potassium remaining at the end of the justamedullary descending limb for 94 +/- 11% to 38 +/- 3% (P less than 0.001). The latter value is not significantly different from the fraction of filtered sodium remaining (36 +/- 4%) and suggests that net addition of potassium to the pars recta or descending limb was completely abolished. A correlation was observed between the fraction of filtered potassium remaining at the end of the descending limb and either urinary potassium excretion (P less than 0.001) or urinary potassium concentration(P less than 0.001) in the contralateral unexposed kidney. These results lend further support to the hypothesis of medullary recycling of potassium.

Effect of chronic potassium loading on potassium secretion by the pars recta or descending limb of the juxtamedullary nephron in the rat.

Recently we demonstrated potassium secretion by the pars recta or by the descending limb of the juxtamedullary nephron. The purpose of this present investigation is to study the effect of a chronic high-potassium intake on this phenomenon. Fractional reabsorption of water and sodium by the juxtamedullary proximal nephron was decreased when compared to that in normal hydropenic rats. There was a striking increase in the fraction of filtered potassium at the end of the juxtamedullary descending limb from 94+/11% to 180+/18%, which was principally a result of enhanced potassium secretion. When the concentration of potassium in the collecting tubule fluid of potassium-loaded rats was reduced after the administration of amiloride, a sharp fall was observed in the amount of potassium which reached the end of the descending limb (64+/8%). A direct correlation was observed between the fraction of filtered potassium at the descending limb and the potassium concentration in the final urine (P less than 0.001). The findings suggest that potassium, like urea, normally undergoes medullary recycling, which is enhanced by chronic potassium loading.

Micropuncture study of water and electrolyte movements along the loop of Henle in psammomys with special reference to magnesium, calcium and phosphorus.

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.

Ostnatal development of renal function: micropuncture and clearance studies in the dog.

Postnatal renal development was studied in dogs between 2 and 77 days. Single, superficial nephrons were evaluated by micropuncture, concurrently with measurements of total renal function and morphometric analyses in the same animals. Glomerular filtration rate for the entire kidney increased linearly from 0.13 ml/min per g kidney weight at 2 days to 0.91 at 77 days. Extraction of p-aminohippurate increased from about 20 to 80%, and renal plasma flow per g kidney weight, measured as Cpah/Epah, increased threefold during the same period. Filtration fraction increased to the mature value during the first half of the postnatal period studied. The clearance of urea per unit of renal mass increased with age, whereas the fraction of filtered urea reabsorbed declined during the early part of the postnatal period. The pattern of fractional urea reabsorption may be due mainly to increased medullary recycling of urea and to a rise in the reabsorption of water from the medullary collecting duct. Urine osmolality was higher than plasma from birth onward and rose with age. Osmolal equality of collecting duct fluid and medullary interstitium reflected mature vasopressin (ADH)-induced water permeability. The rise in urinary concentration was predominantly due to increasing medullary sequestration of urea. Glomerular filtration rate of the superficial nephron increased from 3.2 nl/min at 21 days, when subcapsular nephrons were uniformly patent, to 23.1 at 77 days. Despite this rise in filtered load, fractional reabsorption of sodium and water in superficial proximal tubules was constant and at the mature level from the onset of intratubular perfusion. Changes in arterial plasma protein concentration, in filtration fraction, and in the hydrostatic pressure gradient between proximal tubule and peritubular capillary may interact to maintain glomerulotubular balance. The data, together with results of an accompanying morphological study, demonstrate a sequence of coordinated changes during postnatal renal maturation.

Micropuncture study of water, electrolytes, and urea movements along the loops of henle in psammomys.

The mechanism by which the osmotic pressure increases in tubular fluid along the descending limb of the loop of Henle was examined in Psammomys undergoing salt diuresis. In two series of experiments, micropuncture samples were collected either from proximal and distal convolutions at the surface of the cortex, or from loops of Henle and collecting ducts at the surface of the extrarenal part of the papilla. Inulin-(3)H, urea-(14)C, Na(+), and K(+) concentrations, as well as osmotic pressure, were determined in all micropuncture samples.Net movements of water along the descending and ascending limbs of the loop could not be deduced by comparing inulin data obtained from convoluted tubules and from loops of Henle, since there appeared to be a large difference in the filtration rate of the superficial glomeruli (9 nl/min) and the deep ones (21.4 nl/min) under the conditions of these experiments. The results indicate that no large net movement of water occurred along the loop since a) only 23% of the filtrate was reabsorbed along the loop of Henle (including pars recta) of superficial nephrons despite the fact that all these loops reached markedly hypertonic regions; b) there was no positive correlation between (F/P)(In) in early distal samples and the simultaneous osmotic pressure of the urine; c) when (F/P)(In) and (F/P)(Osm) in loop samples were correlated, the increase in inulin concentration accounted only for 15% of the increase in osmotic pressure. Therefore, 85% of the concentrating process taking place along the descending limb must have resulted from net addition of solutes; this was directly supported by Na(+) and K(+) measurements in the loop samples, which showed that, at the tip of the loops, the Na(+) and K(+) flow rates were correlated to the osmotic pressure. Moreover, since the load of Na(+) urea flow rate in superficial early distal tubules was constant and independent of the urinary osmotic pressure, it is suggested that a medullary recycling of both ions occurred between ascending and descending limbs.Urea-(14)C concentration in the loop samples indicates a net addition of urea into the descending limb; the mean and K(+) delivered to the distal superficial tubules was 4.18 times its filtration rate, suggesting a recycling of urea from collecting ducts to Henle's loops. The permeability properties of the wall of the thin descending limb are discussed in relation to the obtained results.