A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
H Sonnenberg
Publications and source records attributed to H Sonnenberg.
Urea handling by the medullary collecting duct of the rat kidney during hydropenia and urea infusion.
Previous micropuncture studies of distal tubule fluid and ureteral urine have indicated a varying degree of urea reabsorption in the collecting duct. In the present experiments the microcatheterization technique was used to directly determine urea, Na, K, total solute and fluid reabsorption along the length of the medullary collecting duct in anesthetized hydropenic rats and in rats given low dose urea infusion (Purea 18.9 mM/l). In hydropenic rats, the remaining fraction of filtered urea did not change significantly along the collecting duct, as indicated both by regression analysis of all samples and by comparison of paired samples from the corticomedullary junction and papillary tip. During low dose urea infusion, urine osmolality increased in proportion to the increase in urea concentration and again there was no net urea reabsorption between the beginning and end of the duct. However, during urea infusion, analysis of samples from the beginning, mid-zone, and end of the collecting duct indicated that urea entry occurred in the proximal portion of the duct (beginning to mid-zone, P less than 0.01) and that urea reabsorption occurred in the distal portion (mid-zone to end, P less than 0.01). The lack of significant net urea reabsorption along the duct despite the excretion of moderately concentrated urine, has despite the excretion of moderately concentrated urine, has implications for the concept of medullary urea recycling and for models of the urinary concentrating mechanism. The finding of functional heterogeneity with respect to urea handling in the collecting duct in vivo, with both reabsorption are secretion being demonstrated, raises the possibility that internal recycling of urea in the medullary collecting duct itself may contribute to maintenance of a high papillary interstitial urea concentration.
Animals↗
A micromethod to measure ammonia.
We have described a simple technique for the measurement of picomoles or nanomoles of ammonium. Samples can be easily processed on the day of an experiment. analysis of 14C-glutamate can be done at a later date by an accurate sensitive and reliable method. We can readily process 50 samples per day. The sensitivity can be increased by using smaller volumes of ammonia-free solutions, prereacting endogenous ammonia with nonradioactive 2-oxoglutarate, and increasing the specific activity of 2-oxoglutarate. The volumes must, however, be very low so as not to diminish the ammonium concentration and thereby limit glutamate formation.
Ammonia↗
Sites of ammonia addition to tubular fluid in rats with chronic metabolic acidosis.
The purpose of this investigation was to determine in which nephron segments ammonia was added to or removed from the lumenal fluid of the rat. Ammonium was measured in proximal and distal tubular fluid samples obtained by micropuncture and in collecting duct fluid samples obtained by microcatheterization. Water abstraction was assessed by examining the tubular fluid-to-plasma inulin concentration, (TF/P)In. In normal or acidotic rats, the vast bulk of the final urine ammonium appeared in the proximal tubular fluid samples. Most of this ammonia was lost, however, in transit from the proximal to the distal tubule so that only 20 to 30% of the excreted ammonium was present at the distal site. Ammonia reentered the lumenal fluid primarily in the cortical collecting duct in acidotic rats and in the medullary collecting duct in normal rats. Although the pattern was qualitatively similar in both groups of rats, the absolute quantity of ammonium in each nephron segment of normal rats was about 10 to 20% of that in acidotic animals.
Acidosis, Renal Tubular↗
Ammonia addition into the medullary collecting duct of the rat.
The purpose of these studies was to determine if ammonia is added directly to the medullary collecting duct of the rat, and if so, to estimate its quantitative contribution to ammonium excretion. Samples of fluid were obtained along the length of the medullary collecting duct by retrograde microcatheterization. To document net addition of ammonium, we measured the ammonium concentration in tubular fluid by an enzymatic isotope technique, and we calculated the degree of fluid reabsorption from the ratio of the inulin concentration in tubular fluid and plasma. The ammonium concentration corrected for water reabsorption ([NH4+]/[TF/P]In) rose progressively from the beginning to the end of the medullary collecting duct, indicating net ammonia addition to this nephron segment. By calculation, it appears that about 40% of the excreted ammonium reached the urine by direct addition of ammonia to the duct fluid.
Ammonia↗
Cardiac atrial factor--an endogenous diuretic?
An extract of rat heart atria causes a saluresis in bioassay rats. When organic acid secretion in the proximal tubule was blocked by probenecid, the saluretic response to the extract was significantly reduced. Similarly, the natriuretic response to acute hypervolemia was reduced by probenecid administration. The data indicate that the atrial natriuretic factor, like the "loop" diuretic drugs, requires proximal tubular secretion for maximal renal activity. Furthermore, the factor may play a role in the renal response to acute blood volume expansion.
Animals↗
Urea secretion in medullary collecting duct of the rat kidney during water and mannitol diuresis.
During steady-state water or mannitol diuresis, the microcatheterization technique was used to study the handling of urea, fluid, sodium, potassium, and total solute along the length of the medullary collecting duct in anesthetized rats. During water diuresis, the remaining fraction of filtered urea increased along the collecting duct as indicated both by regression analysis of all samples and by comparison of paired data from the beginning and end of the duct [(TF/P)urea/In = 43.3 and 50.7%, respectively]. During mannitol diuresis, similar urea entry into the medullary collecting duct was observed, (TF/P)urea/In increasing from 60.7 to 66.5%. Comparison of collecting duct urea handling in proximal and distal segments (beginning to midzone and midzone to papillary tip) suggested that urea entry occurred to a greater extent in the distal portion of the medullary collecting duct. The results demonstrate urea secretion into the medullary collecting duct in diuretic states when urine flow is high and intratubular urea concentration low. Whether urea entry into the collecting duct is an active or passive process cannot be determined from this study, but comparison between urea concentrations in the papillary interstitial fluid and in the urine or tubular fluid raises the possibility of an active urea secretory mechanism in the collecting duct.
Absorption↗
Characterization of the natriuretic activity in the plasma of hypervolaemic rats.
1. Plasma from hypervolaemic rats was fractionated on a G-200 Sephadex column. In addition to three different protein peaks, a fourth non-protein fraction was obtained. Each of the four peaks was desalted, freeze-dried, reconsituted and injected into normal anaesthetized rats. Significant natriuretic responses resulted, from injection, of the middle protein peak and of the small-molecular-weight peak. It was concluded that a natriuretic humoral factor was present in the blood of hypervolaemic rats, and that this factor was of low molecular weight but normally occurred bound to plasma protein. 2. The renal response to injection of non-protein fraction, obtained from either hypervolaemic donors or from iso- or hypo-volaemic donors, was compared in two groups of bioassay rats to test whether the natriuretic factor was present only in plasma of the blood-volume-expanded animals. Both types of reconstituted fraction caused diuresis, natriuresis and kaliuresis in bioassay animals. Only the natriuretic response was statistically greater when the fraction obtained from hypervolaemic plasma was used. In addition to non-specific increase in fluid and ion excretion, possibly due to the extraction and/or methodological procedures, these results demonstrate that blood-volume expansion releases a humoral natriuretic factor into plasma. Since there were no increases in filtration rate, the factor specifically inhibited tubular sodium reabsorption. 3. To determine the maximum possible effect of the non-protein factor, the dose given to bioassay rats was tripled. There was no further increase in sodium excretion, indicating that the effect was quantitatively limited and suggesting that the physiological importance of natriuretic hormone lies in long-term regulation of body-fluid balance.
Animals↗
Renal blood flow distribution measured by microspheres during isovolemic hematocrit alteration in rats.
The distribution of 15-micron microspheres was measured in rat kidneys before and after the animals had undergone either isovolemic hematocrit increase or isovolemic hematocrit decrease. Raising the systemic arterial hematocrit from 46 +/- 1% (mean +/- SEM) to 59 +/- 1% caused a significant decrease in the rate of urinary sodium and potassium excretion (UNaV, UKV), but not significant changes in total renal blood flow (RBF), filtration fraction (FF), outer cortical flow, inner cortical flow, or rate of urinary volume excretion (V). Fractional sodium excretion was also unchanged suggesting that the decreased UNAV was the result of a decreased glomerular filtration rate (GFR). The measured decrease in GFR was not statistically significant. Lowering the systemic hematocrit from 45 +/- 1% to 33 +/- 1% caused a significant fall in FF as well as significant increases in the rate of urine volume excretion (V), UNaV, UKV, and GRF. There was a significant increase in RBF but again no change in the flow distribution between inner and outer cortex. The findings show that hematocrit alterations alone do not immediately lead to a redistribution of blood flow between inner and outer cortex of the rat kidney.
Animals↗
Comparison of micropuncture of microcatheterization in papillary collecting duct.
Collecting duct transport of fluid, sodium and potassium was studied in rats infused with Ringer solution (5 ml . 100 g body wt-1 . h-1). A terminal segment of surface collecting duct in the exposed papilla was catheterized as far upstream as possible under visual observation. After fluid sampling the same duct was punctured at the same site with a glass micropipette and a second sample was taken. Samples were then obtained from the opening of the duct at the papilla tip by both catheter and micropipette. No significant difference between the two collection sites was found in the fraction of filtered sodium, potassium, or fluid remaining in the tubules, independent of the sampling technique used, indicating that volume expansion inhibited salt and water reabsorption. Although fractional fluid and sodium remainders were slighlty higher and potassium remainder lower in upstream micropuncture samples compared to catheterization samples, the good correlation between collections obtained with both techniques suggests that both are equally valid as indicators of transport in terminal collecting ducts.
Animals↗
Medullary collecting duct function in the remnant kidney before and after volume expansion.
The role of the medullary collecting ducts (CD) in the regulation of water and electrolyte excretion by the remnant kidney has not been determined. Medullary CD function was therefore studied by the microcatheterization technique during hydropenia and after volume expansion with an isotonic saline load in rats with sham-operated normal kidney (stage I), remnant kidney (stage II), remnant kidney after contralateral nephrectomy (stage III), and sham-operated normal kidney after contralateral nephrectomy (stage-III control). Sodium, potassium, water, and solute reabsorption along the medullary CD were not altered in stage II during hydropenia when compared to normal control (stage I), but water reabsorption proximal to the medullary CD was decreased. In stage III, where the uremia was mild (BUN, 41 mg/dl), the fractions of the filtered load of sodium (72%) and water (62%) which were reabsorbed along the medullary CD were reduced in comparison to stage II (94% and 83%, respectively), stage I, or stage-III control. The fraction of filtered potassium entering the medullary CD was increased to 53% in stage III, compared to 16% in stage II, and 10 or 11% in stage I or stage-III control. No change in the fraction of filtered potassium remaining along the collecting ducts was observed. After volume expansion, there was no significant change in the fraction of filtered sodium and water remaining along the medullary CD in stage I, II, or III. The greater fractional excretion in stage III resulted from decreased reabsorption in more proximal nephron segments. The results indicate that (a) during hydropenia, fractional reabsorption of sodium and water is decreased along the medullary CD of the stage-III remnant kidney in the presence of mild uremia, (b) the increased fractional excretion of potassium in the remnant kidney with uremia is not determined by altered potassium handling in the medullary CD but occurs proximal to this nephron segment, and (c) extracellular fluid volume expansion with isotonic saline results in similar inhibition of fractional sodium and water reabsorption in the collecting ducts of both remnant and normal kidneys.
Animals↗
Questions and replies: role of the collecting tubule in fluid, sodium, and potassium balance.
In terms of day-to-day regulation of fluid and electrolyte balance, the collecting tubule system appears to occupy a paramount position among segments of the renal tubule. Controversy has arisen concerning the quantitative contribution by the collecting tubule system to the regulation of individual solute excretion, which in part may be due to differences among the investigative techniques employed. In this Editorial Review, R. L. Jamison summarizes current views on the function of the collecting tubule system, particularly with regard to regulation of sodium and potassium excretion, and then poses seven questions pertaining to this topic. H. Sonnenberg, who has revived the microcatheterization technique, and J. H. Stein, whose group has employed the micropuncture method, respond to these questions. The key issues addressed are: 1) the principal factors that influence transtubular movement of sodium and potassium across the collecting tubule; 2) the limitations and potential artifacts of the microcatheterization and micropuncture techniques when used to examine the function of the collecting tubule; 3) apparent discrepancies among results obtained by micropuncture in vivo, microcatheterization in vivo, and microperfusion in vitro of the collecting tubule; and 4) major unresolved questions concerning the function of the collecting tubule.
Animals↗
Effects of furosemide, acetazolamide, and mannitol on medullary collecting-duct function in the rat kidney.
Explore the source record for details and available documents.
Acetazolamide↗
Effect of adrenalectomy on medullary collecting-duct function in rats before and during blood volume expansion.
Adrenalectomized rats, kept on tap water for 3 days and infused with the glucocorticoid dexamethasone during the experiment, were compared to similarly treated sham-operated rats. Using the microcatheterization technique, reabsorption of fluid, sodium and potassium in the medullary collecting duct was studied before and after infusion of donor blood (2.3% of body weight). Before intravascular volume expansion sodium excretion in adrenalectomized rats was greater than in sham-operated ones. Extensive overlap between the two groups made this difference not statistically significant. However, the fraction of filtered sodium excreted was significantly greater after adrenalectomy, indicating the expected tubular transport defect. Fluid reabsorption from the medullary collecting-duct system was comparable in both series. Adrenalectomy did not inhibit net sodium reabsorption from the inner medullary duct, although reduction of Na transport in the outer medullary collecting system could be inferred. Renal excretion of potassium was not associated with net K secretion in the collecting duct in either group. During hypervolemia induced by intravenous infusion of donor blood, marked diuresis, natriuresis and kaliuresis were observed in all animals, associated with inhibition of net fluid and sodium reabsorption along the collecting system in both inner and outer medulla. Small, but statistically significant secretion of potassium became evident. The relatively reduced renal response in adrenalectomized animals could be attributed in part to a decreased filtered load compared to sham-operated rats. It is concluded: (1) that lack of mineralocorticoid does not prevent the normal fluid and sodium reabsorption from the lumen of the inner medullary collecting system, and (2) that the inhibition of this reabsorption consequent to hypervolemia is independent of changes in plasma aldosterone levels.
Adrenalectomy↗
Intrarenal hemodynamics in cross-circulated hypervolemic and isovolemic rats.
The microsphere technique was used to measure renal blood flow and intrarenal flow distribution in cross-circulated pairs of rats. One rat of each pair was made hypervolemic by infusion of blood (2.3% of body weight), followed by intravenous reinfusion to urine to maintain intravascular expansion. The other rat of each pair, which also was urine-reinfused, was kept isvolemic throughout the experiment. As shown previously, blood infusion resulted in a large diuretic and natriuretic response in the hypervolemic partner, while a smaller but statistically significant response occurred in the isovolemic partner. Total renal blood flow did not change in the expanded rats and fell slightly but not significantly in the nonexpanded ones. Blood volume expansion was associated with a significant shift in microsphere concentration from outer to inner cortex. This shift was not, however, correlated with the magnitude of the renal response. The transferred natriuresis in isovolemic partners was not associated with any change in microsphere distribution. We conclude therefore, that redistribution of blood flow to the inner cortex, although a feature of intravascular expansion, is not the primary determinant of volume natriuresis. In addition, the natriuretic activity which develops in the blood of hypervolemic rats can reduce sodium reabsorption in isovolemic rats without intrarenal hemodynamic changes.
Animals↗
Collecting duct function in deoxycorticosterone acetate-escaped, normal, and salt-deprived rats. Response to hypervolemia.
The microcatheterization technique was used to study reabsorption of fluid, sodium, and potassium in the medullary collecting duct in chronically deoxycorticosterone acetate (DOCA)-treated and salt-loaded rats, as well as in normal and chronically salt-deprived (NaD) rats, before and after infusion of donor blood (33% of estimated circulating volume). Before expansion, urinary sodium excretion was highest in DOCA rats, intermediate in normal, and lowest in low salt rats. Significant collecting duct reabsorption was found in NaD, normal, and DOCA groups. In contrast to sodium, no net transport of potassium was found in any series. During intravascular expansion, increased renal excretion of fluid and sodium was observed uniformly in both DOCA and normal groups, whereas a diuretic response was found in five of seven rats, and a natriuretic response in four of seven rats of the NaD group. Natriuresis of DOCA rats was significantly greater than that of either normal or responding NaD rats. Diuresis and natriuresis in all three series were assocaited with complete inhibition of fluid and sodium reabsorption from the lumen of the medullary collecting duct, whereas such reabsorption persisted in nonresponding low salt rats. Increased sodium excretion in DOCA rats in comparison to the other two series could be explained by enhanced intratubular delivery of the ion to the medullary collecting system. I conclude that the renal response to acute blood volume expansion is due primarily to complete inhibition of both fluid and sodium reabsorption in the medullary collecting duct, but that differences in tubular delivery may modify the resulting diuresis and natriuresis.
Animals↗
The role of the medullary collecting ducts in postobstructive diuresis.
Medullary collecting duct function was studied by direct microcatheterization techniques in rats undergoing postobstructive diuresis. Significant net addition of water and sodium to the duct was demonstrated during postobstructive diuresis after relief of 24-h bilateral ureteral ligation. This striking abnormality in function was associated with reduced delivery of sodium and water to the collecting duct compared to sham-operated controls. To examine the role of circulating factors in this phenomenon, another group of rats was studied that underwent 24 h of total urine reinfusion into the femoral vein. Natriuresis and diuresis were similar to the postobstructive group, but absolute collecting duct reabsorption of sodium and water was normal. The natriuresis and diuresis in rats with urine reinfusion resulted from increased delivery of fluid and sodium to the medullary collecting duct. A third group of rats was studied with 24-h unilateral ureteral ligation as well as urine reinfusion from the contralateral normal kidney. Without urine reinfusion there was no diuresis-natriuresis but with urine reinfusion the diuresis and natriuresis after relief of unilateral obstruction was similar to that after relief of bilateral obstruction. Moreover, net addition of sodium and no significant water reabsorption were demonstrated in the medullary collecting duct of such animals. The results indicate that (a) the medullary collecting duct is the critical nephron segment affected by ureteral obstruction, since postobstructive diuresis occurred despite reduced delivery of fluid from the more proximal nephron; (b) the net addition of sodium to the medullary collecting duct observed during postobstructive diuresis is probably a direct effect of obstruction, since it was found during postobstructive diuresis after relief of bilateral or unilateral ureteral ligation, but not with urine reinfusion alone; and (c) blood-borne factors are important in the development of postobstructive natriuresis and diuresis, and probably act by increasing the fraction of filtered sodium and water delivered from the proximal and distal tubule to the collecting duct.
Absorption↗
Time course of onset and decay of humoral natriuretic activity in the rat.
The natriuretic mechanism.tic activity shown in earlier cross-circulation experiments to develop in the blood of rats undergoing sustained vascular expansion has been further characterized. Following whole blood infusion and urine reinfusion of the donor rat, a cross-circulated isovolaemic partner exhibits a natriuresis of gradual onset, requiring 60-80 min to reach a peak (0.04-3.24 muequiv./min per gram kidney weight). The gradual feature of recipient natriuresis was unchanged by infusing the donor rat 1 h prior to cross-circulation. Once developed, the recipient natriuresis was sustained when fluid depletion by the renal response was prevented, but was reversible with a half-life of about 30 min on interruption of the cross-circulation; reconnection of cross-circulation promptly restored recipient natriuresis. No significant natriuresis (0.04-0.16 muequiv/min per gram kidney weight) occurred in the recipients if the donors in comparable cross-circulations were not infused. These findings confirm that a natriuretic activity develops in the blood as a consequence of vascular expansion, and reveal that the activity has a slowly developing and reversible action on the renal natriure
Animals↗