bluuebunny/crossref_metadata_2025 huggingface dataset:
Glomerular ultrafiltration in the pseudopregnant rat
Authors: Baylis C.
Published: December 2017

Whole kidney and single nephron indices of glomerular ultrafiltration were measured by clearance and micropuncture techniques in anesthetized virgin, 9-day pregnant, and 9-day pseudopregnant Munich-Wistar rats. Whole kidney glomerular filtration rate (GFR) and single nephron glomerular filtration rate (SNGFR) were elevated in pregnant and pseudopregnant rats compared with virgins (0.78 +/- 0.05, 0.75 +/- 0.06 vs. 0.57 +/- 0.03 ml/min, P less than 0.005 and P less than 0.001; 32.1 +/- 2.5, 30.0 +/- 2.8 vs. 22.1 +/- 2.0 nl/min, P less than 0.01 and P less than 0.05, respectively). Total renal plasma flow rate (RPF) and single glomerular plasma flow rate (QA) were also increased in pregnant and pseudopregnant rats compared to virgins (3.05 +/- 0.19, 2.90 +2- 0.24 vs. 2.28 +/- 0.21 ml/min, P less than 0.01 and P less than 0.05; 109.0 +/- 15.8, 100.4 +/- 12.8 vs. 68.0 +/- 6.9 nl/min, both P less thn 0.05). There was little difference in the other determinants of ultrafiltration among the three groups. Plasma volume was measured in separate experiments and was higher in pregnant and pseudopregnant rats compared with virgins (9.4 +/- 0.2, 9.8 +/- 0.4 vs. 8.4 +/- 0.3 ml, P less than 0.01 and P less than 0.05, respectively). The gestational increase in GFR in the rat occurs as the result of increased RPF, which is due to both plasma volume expansion and renal vasodilation. Since the changes in renal hemodynamics seen in pseudopregnancy were almost identical to those occurring in pregnant rats, the early stimulus to increased GFR must be maternal and not fetoplacental in origin.
Renal carbonic anhydrase
Authors: Dobyan D. C. , Bulger R. E.
Published: December 2017

Carbonic anhydrase is a zinc metalloenzyme widely distributed throughout the tissues of the body. This enzyme exists in a number of isozymic forms in most mammalian species. Significant advances over the past decade have been made in characterizing the nature of renal carbonic anhydrase. In the kidney, this enzyme is thought to play a pivotal role in urinary acidification and bicarbonate reabsorption. Two distinct isozymes of carbonic anhydrase have now been identified in the mammalian kidney. A soluble cytoplasmic form, similar if not identical to human erythrocyte carbonic anhydrase C, accounts for the bulk of the renal carbonic anhydrase activity. In addition, a membrane-bound form constituting only about 2--5% of the renal activity has been found in the brush border and basolateral fractions of kidney homogenates. The histochemical and immunocytochemical localization of these isozymes along the nephron and collecting duct system of various mammalian species suggests that marked heterogeneity exists. The Editorial Review examines the biochemical and morphological approaches that have been used to elucidate the nature of renal carbonic anhydrase and to assess its distribution along the urinary tubule. Possible physiological roles for the renal carbonic anhydrases are considered for the different segments of the nephron and collecting duct system.
Distal acidification in the rabbit: role of diet and blood pH
Authors: Cruz-Soto M. , Batlle D. , Sabatini S. , Arruda J. A. , Kurtzman N. A.
Published: December 2017

A distal acidification defect is said to exist in rabbits because this species does not achieve a normal urine minus blood (U-B) PCO2 gradient in response to sodium bicarbonate infusion. This observation contrasts with data derived from studies in isolated rabbit cortical collecting tubules that have shown an acidifying capacity when the tubules were obtained from acidotic animals. The present study was designed to examine the role of diet and blood pH on distal acidification in the rabbit. Maximal alkalinization of the urine by acute sodium bicarbonate infusion was associated with a low U-B PCO2 gradient (0.7 +/- 2.1 mmHg). Rabbits made acidotic by ammonium chloride administration for 1 wk achieved a substantial U-B PCO2 gradient (29 +/- 5 mmHg) in response to neutral sodium phosphate infusion. To further evaluate the role of blood pH on the ability to raise U-B PCO2 gradient, rabbits and rats made acidotic by chronic ammonium chloride administration were studied. Neutral sodium phosphate was then infused to stimulate distal acidification. At comparable levels of urinary phosphate concentration and blood pH, acidotic rabbits were able to achieve a U-B PCO2 (50 +/- 7 mmHg) comparable with that of acidotic rats (48 +/- 8.3 mmHg). These data show that the failure of rabbits to raise U-B PCO2 gradient can be partially corrected by prior exposure to acid in the diet and further corrected by maintaining the blood pH within the acidotic range.
Kinetics, competition, and selectivity of tubular absorption of proteins
Authors: Sumpio B. E. , Maack T.
Published: December 2017

Tubular absorption (T) of two cationic proteins, lysozyme (LZM) and cytochrome c (CYT c), and two anionic proteins, beta 2-microglobulin (beta 2M) and 125I-labeled human growth hormone (hGH), was studied in the isolated perfused rat kidney. All four proteins are extensively filtered and, at low loads, almost completely absorbed by the tubular epithelium. TLZM and TCYT c is a saturable process of high capacity (Tm) and low apparent affinity. (Tm)LZM was two orders of magnitude larger than (Tm)CYT c. LZM inhibited TCYT c in a dose-dependent and reversible manner. Saturating loads of CYT c failed to inhibit T beta 2M and ThGH. Saturation, selectivity, and competition is explained on the basis of a model that incorporates adsorption of protein to microvilli as well as geometric and electrical constraints on the access of filtered proteins to endocytic sites at the base of the microvilli. Tubular absorption of all proteins is decreased by inhibitors of the formation and/or internalization of endocytic vesicles (iodoacetate and cytochalasin B). However, lysine (5 mM) and low perfusate calcium concentration (0.5 mM) inhibited T beta 2M but not TCYT c and ThGH. The selective effect of 5 mM lysine, which causes morphologic damage in initial portions of the proximal convoluted tubule, may be due to preferential or exclusive absorption of beta 2 M in this portion of the nephron. The results as a whole demonstrate that in addition to net charge other structural features of the protein molecule and of the luminal wall of proximal tubules may be important determinants of the efficiency and capacity of the tubular absorption of filtered proteins.
Glucose transport in chronically altered rat nephrons
Authors: Kramp R. A. , Lorentz W. B.
Published: December 2017

Microinjection experiments were performed in anesthetized rats to study the tubular absorptive capacity for glucose (TG) in normal and chronically altered tubules, i.e., tubules that sustained anatomical repair and compensatory changes of their previously normal configuration after acute damage. TG was complete when the glucose load injected in normal or altered early or late proximal convolutions was less than or equal to 1.5 or less than or equal to 10 pmol . s-1, respectively. In normal tubules, TmG was 10 and 5 pmol . s-1 after early and late proximal microinjections, respectively. After early proximal microinjections in altered tubules, different levels of TmG were found. They related to the degree of compensatory growth. TmG was approximately 12, 24, or 35 pmol . s-1, respectively, in altered tubules with minor, moderate, or major compensatory growth. After late proximal microinjections, TmG was 15 pmol . s-1. TG variability was greater in altered than in normal tubules. Correlation between structural and functional compensatory changes was thus demonstrated. Furthermore, an important, albeit latent, absorptive capacity for glucose of the proximal straight tubule was found.
Cell volume regulation in the proximal convoluted tubule
Authors: Gagnon J. , Ouimet D. , Nguyen H. , Laprade R. , Le Grimellec C. , Carriere S. , Cardinal J.
Published: December 2017

To evaluate the effect of hyper- and hypotonicity on proximal convoluted tubule (PCT) cell volume, nonperfused PCT were studied in vitro with hypertonic solutions containing sodium chloride, urea, or mannitol (450 mosmol/kg H2O) and with hypotonic low sodium chloride solutions (160 mosmol/kg H2O). When the tubules were subjected to hypertonic peritubular solutions containing NaCl, cell volume immediately decreased by 15.5% and remained constant throughout the experimental period (60 min). With mannitol, the initial decrease was identical to that with NaCl (17.7%), but the PCT volume increased slightly during the experimental period. With urea, the decrease in cell volume was smaller (7%) and transient. In hypotonicity, the PCT swelled rapidly, but this swelling was followed by a rapid regulatory phase in which PCT volume nearly returned to control values after less than 10 min. With a potassium-free peritubular medium or 10(-3) M ouabain, the regulatory phase of hypotonicity completely disappeared, whereas the cells did not maintain their reduced volume in NaCl-induced hypertonicity. These results suggest that Na-K-ATPase plays an important role in the maintenance of a reduced cellular volume in hypertonicity and in the regulatory phase of hypotonicity, probably by an active extrusion of sodium and water from the cell.
Renal function and renal afferent and efferent nerve activity
Authors: Moss N. G.
Published: December 2017

Recent microperfusion studies have fully substantiated the direct action of catecholamines on renal tubular reabsorptive rates. Surprisingly, these techniques have not provided consistent information on the nature of the adrenoceptor responsible for the stimulation of proximal tubular reabsorption. Both alpha- and beta-receptors have been favored for this role. These techniques have confirmed earlier reports that dopamine may have a direct natriuretic action on the renal tubules. The demonstration that renal efferent nerves contain both noradrenergic and dopaminergic fibers lends further support for the participation of dopamine in the regulation of salt and water excretion. Efferent renal nerve activity is modulated by a number of different afferent inputs to the central nervous system. One of these is the renal afferent innervation, which is composed of both chemoreceptor and mechanoreceptor fibers. A number of different reflexes that affect efferent renal nerve activity have been identified by electrical stimulation of renal afferent nerves or by selective stimulation of renal mechanoreceptors and chemoreceptors. These renorenal reflexes may have importance in the coordination of excretory activity between the two kidneys. Studies of these aspects of renal nerve function are reviewed. The importance of the renal nerves in conscious animals is also discussed in the light of evidence that their influence on renal function may be more apparent in abnormal or pathological circumstances.
Angiotensin-mediated alterations in nephron function in Goldblatt hypertensive rats
Authors: Huang W. C. , Ploth D. W. , Navar L. G.
Published: December 2017

The present study was performed to evaluate superficial nephron responses of the nonclipped kidney to angiotensin I converting enzyme inhibitor (CEI) (SQ 20,881, 3 mg . kg-1 . h-1) in two-kidney, one-clip Goldblatt hypertensive (GH) rats. Late proximal and early distal tubule collections were obtained before and during CEI. Significant increases in glomerular filtration rate, urine flow, sodium excretion, proximal and distal tubule flow rates, and single nephron glomerular filtration rate (from 24.6 +/- 1.7 to 27.5 +/- 1.6 nl/min) occurred despite reductions in arterial blood pressure (from 160 +/- 5 to 137 +/- 6 mmHg) during CEI. Proximal tubule absolute and fractional reabsorption of fluid, chloride, and total solute decreased significantly. In the nephron segment between the two collection sites, there were increases in absolute but decreases in fractional reabsorption. At the distal tubule level, fractional reabsorption but not absolute reabsorption decreased significantly. Proximal and distal tubule hydrostatic pressures increased significantly while peritubular capillary pressure decreased slightly. Responses following inhibition of angiotensin II formation suggest that there exists an angiotensin II-mediated enhancement in tubular reabsorption in the nonclipped kidney of Goldblatt hypertensive rats.
Decreased distal acidification in acute hypercapnia in the dog
Authors: Adrogue H. J. , Stinebaugh B. J. , Gougoux A. , Lemieux G. , Vinay P. , Tam S. C. , Goldstein M. B. , Halperin M. L.
Published: December 2017

The present studies evaluate the effect of acute hypercapnia on distal nephron H+ secretion (DNH+S) in vivo by means of the urine-blood PCO2 difference (U-B PCO2) in alkaline urine. Bicarbonaturia was induced by either a sodium bicarbonate infusion or L-lysine administration. Our results demonstrate that the U-B PCO2, as a function of the urinary bicarbonate concentration, was significantly lower during acute respiratory acidosis; this effect was not dependent on changes in glomerular filtration rate and/or fractional excretion of sodium, potassium, and chloride. Infusion of the sodium salts of sulfate, a nonreabsorbable anion, did not correct the diminished U-B PCO2. Amiloride caused the U-B PCO2 to fall in normocapnic dogs but not in hypercapnic dogs. When hypercapnia was superimposed in dogs with extracellular fluid volume contraction, there were no changes in the U-B PCO2. This study indicates that acute hypercapnia in the intact dog decreases DNH+S and is compatible with an effect of hypercapnia on the voltage-dependent component of urine acidification. The mechanism appears to be direct rather than secondary to factors that influence the rate of sodium delivery to the distal nephron.
Role of the electrochemical gradient for Na+ in D-glucose transport by mullet kidney
Authors: Lee S. H. , Pritchard J. B.
Published: December 2017

Brush border membrane vesicles were prepared from striped mullet (Mugil cephalus) kidney. As judged by the marker enzyme activities, these membranes were enriched 10- to 15-fold compared with the initial homogenate. Uptake of D-glucose was phlorizin sensitive and Na+ dependent. L-glucose uptake was unaffected by either phlorizin or Na+. D-Glucose uptake reflected entry into the osmotically active intravesicular space, not binding to the membranes. When Na+ was increased from 25 to 100 mM, the maximum velocity of glucose uptake was increased from 92 to 423 pmol . s-1 . mg protein-1, whereas the apparent Km (1.27 +/- 0.23) was not altered as Na+ increased. 22Na+ uptake by these membrane vesicles was stimulated by D-glucose and inhibited by phlorizin. These results indicated that Na+ and glucose entered the vesicles via a cotransport process. Consistent with this interpretation, it was possible to show that glucose uptake could be driven by either the chemical or electrical component of the Na+ electrochemical gradient and that the contributions of these two components were additive when both were present. Finally, it was shown that the coupling ratio between Na+ and glucose was approximately 1:1. Accordingly, these results indicate that reabsorption of D-glucose across the brush border membranes is coupled to the transmembrane electrochemical gradient of sodium ions.
Evidence for tubuloglomerular feedback in juxtamedullary nephrons of young rats
Authors: Muller-Suur R. , Ulfendahl H. R. , Persson A. E.
Published: December 2017

To determine whether the filtration rate of juxtamedullary nephrons is regulated by tubuloglomerular feedback (TGF), we developed two micropuncture techniques suitable for the papilla of young rats. One consisted of measuring the tubular flow in descending limbs of Henle loops (VDLH) while the ascending limbs of the loop of Henle (ALH) were perfused at various rates with three different solutions: modified Ringer, artificial Henle loop solution, and Ringer containing 10(-4) M furosemide. SNGFR was also measured in several juxtamedullary nephrons. The other protocol consisted of measuring the tubular stop-flow pressure (PSF) in descending limbs of the loop of Henle upstream to a wax block. Distal to the block Ringer was perfused at various rates through ALH. Our results provide the first evidence of a TGF response in juxtamedullary nephrons. VDLH and SNGFR decreased during Ringer perfusion to 42 +/- 4 and 44 +/- 4% of their values at zero perfusion. The same pattern was observed using Henle loop solution as perfusate, whereas with furosemide VDLH did not change. The maximal decrease in PSF was 14.1 +/- 1.4 mmHg. The perfusion rate necessary to induce a half-maximal PSF decrease was 9.1 +/- 0.9 nl/min. Similar micropuncture techniques were used in proximal tubules of surface nephrons in these rats, which in comparison to the deep nephrons showed smaller feedback responses. The mechanism seems to be active at physiological nephron flow rates in both nephron populations. Thus, TGF can exert its effect on GFR of the whole kidney by acting in both deep and surface nephrons.
Renal response to four hours of biliary obstruction in the dog
Authors: Levy M. , Finestone H.
Published: December 2017

Clearance studies were performed in anesthetized dogs before and 4 h after the acute obstruction of the common bile duct (ABDL). ABDL was not associated with any change in systemic hemodynamics or plasma volume. Glomerular filtration rate (GFR) rose by 15.3%, PAH clearance by 13.3%, and renal blood flow by 13% (all values significant at P less than 0.05). Fractional excretion rates of water and sodium rose from 0.29 to 1.1 and from 0.21 to 0.76%, respectively (P less than 0.05). These changes in renal function were associated with a failure of bile excretion rather than distension of the biliary tree or failure of bile to enter the duodenum. They did not depend on intact hepatic nerves, alteration of hepatic perfusion, or the release of gastrointestinal vasoactive peptides. The increment in renal perfusion was maintained for 2-3 days before returning to baseline levels. Several lines of evidence suggested that factors influencing the renal tubule and the renal microcirculation might be separate in nature: e.g., urinary sodium excretion (UNaV) could increase without a change in GFR; if ABDL was relieved, delta UNaV and delta GFR returned to base line with different time courses; and controlling perfusion to the left kidney during ABDL reduced but did not abolish the increase in UNaV. Both effects could be transferred to recipient dogs by cross-perfusion. We have demonstrated, therefore, that 4 h of ABDL may significantly influence renal function through the appearance of humoral factors in the circulation.
Evidence for an inhibitor of renal urate and PAH secretion in rabbit blood
Authors: Tanner R. J. , Chonko A. M. , Edwards R. M. , Grantham J. J.
Published: December 2017

Results of previous studies of urate secretion in isolated perfused S2 segments of the rabbit proximal tubule suggested that a bath of rabbit serum may inhibit urate transport in comparison to a synthetic medium. In the current study we tested for a urate transport inhibitor by determining the steady-state tissue-to-medium ratio (T/M) of [14C]urate in nonperfused S2 segments during incubation in synthetic medium (BSA-Burg) and commercial rabbit serum (RS-PF). With 80-120 microM urate in the bath the T/M ratio was 7.66 +/- 0.53 (n = 29) in BSA-Burg and 5.29 +/- 0.40 (n = 29) in RS-PF. RS-PF decreased the influx of urate into the cells but had no effect on urate efflux. Freshly drawn rabbit serum and plasma also inhibited urate accumulation, and the inhibition was reversible. p-Aminohippurate accumulation was inhibited by RS-PF, but tetraethylammonium bromide uptake was not. RS-PF inhibited transepithelial secretion of urate and PAH, but net fluid absorption was not decreased. The inhibitory material in rabbit serum could not be removed by extensive dialysis (14,000-dalton exclusion), by ultrafiltration (50,000-dalton exclusion), or by charcoal or ethanol extraction. Inhibitory activity was detected in both albumin and globulin fractions of rabbit serum. The relation between bath and intracellular urate concentrations of nonperfused tubules in rabbit serum was sigmoidal, whereas the relation in the BSA-Burg medium was more nearly hyperbolic. We conclude that organic anion transport in rabbit S2 segments is inhibited or suppressed by normal serum and suggest that urate secretion and excretion may be subject to allosteric modification by serum proteins.
Specificity and modes of the anion exchanger in dog renal microvillus membranes
Authors: Guggino S. E. , Martin G. J. , Aronson P. S.
Published: December 2017

The transport of various organic anions via the pathway that mediates the exchange of urate or p-aminohippurate (PAH) for OH- or Cl- in dog renal microvillus membrane vesicles was investigated. The pH gradient-stimulated uptakes of tracer urate and PAH were significantly inhibited by 5 mM PAH, n-valerate, lactate, beta-hydroxybutyrate, pyruvate, acetoacetate, maleate, succinate, alpha-ketoglutarate, oxaloacetate, and cis-aconitate but not by 5 mM acetate, malate, oxalate, or citrate. the pH dependence of inhibition suggested that it was in their monovalent forms that these acid anions interacted with the urate exchange pathway. Outwardly directed gradients of succinate, lactate, and PAH stimulated uphill urate accumulation. Imposition of an inside-alkaline pH gradient stimulated the uphill accumulation of lactate and succinate. Na+ cotransport pathways for lactate and succinate were also present. In the presence of an inwardly directed Na+ gradient, lactate stimulated the uphill accumulation of urate, indicating that the pathways mediating Na+-lactate cotransport and lactate-urate exchange coexisted in at least some membrane vesicles. We conclude that the anion exchange pathway for urate in dog renal microvillus membrane vesicles has affinity for additional organic anions and can function in multiple exchange modes. Exchange of luminal urate or Cl- for intracellular organic anions or OH- is a possible mechanism for effecting uphill anion reabsorption in the proximal tubule.
Angiotensin-dependent renal mechanisms in two-kidney, one-clip renal vascular hypertension
Authors: Ploth D. W.
Published: December 2017

Our understanding of the physiology of the renin-angiotensin system has advanced remarkably in the last decade as a result of the development of several pharmacologic agents that effectively block components of this humoral cascade. The use of these antagonists has also advanced our understanding of the contribution of the renin-angiotensin system to the development and maintenance of two-kidney, one-clip renal vascular hypertension. These antagonists have contributed greatly to the characterization of the systemic hemodynamic changes that occur in this model and, particularly, to the delineation of the behavior of the nonclipped kidney, a previously normal kidney that is subjected acutely to an environment of elevated systemic blood pressure and the input of a variety of other extrinsic influences. This kidney not only allows the blood pressure to increase and persist at elevated levels but appears to actively participate in the development and propagation of the hypertension. Although a variety of mechanisms impinge on the function of the nonclipped kidney in this model, the goal of this review is to analyze the behavior of this kidney and how its functional state is perturbed, primarily by the influence of angiotensin, which is believed to be delivered to it by the systemic circulation.
Calcitonin decreases the renal tubular capacity for phosphate reabsorption
Authors: Zalups R. K. , Knox F. G.
Published: December 2017

The effects of pharmacologic doses of synthetic salmon calcitonin on the renal tubular capacity of phosphate (Pi) transport were determined in the presence and absence of maximally phosphaturic doses of parathyroid hormone (PTH). Thyroparathyroidectomized rats were given graded infusions of Pi (1, 2, and 3 mumol/min) to prevent the hypophosphatemic effects of calcitonin and to determine the maximum transport of Pi for the kidney (TmPi/GFR). The maximum transport of Pi for the rats treated with calcitonin was 2.46 +/- 0.27 mumol/ml. This value was significantly less than that of 3.88 +/- 0.32 mumol/ml (P less than 0.05) for the control animals but was significantly greater than the maximum transport of Pi of 1.16 +/- 0.05 mumol/ml (P less than 0.05) for the rats treated with PTH. Furthermore, there was no significant difference between the maximum transport of Pi for the rats treated with PTH and that of 1.04 +/- 0.05 mumol/ml for the rats treated with PTH plus calcitonin. We conclude that pharmacologic doses of calcitonin decrease the tubular capacity for Pi reabsorption of the kidney and that the effect is significantly smaller than that of maximally phosphaturic doses of PTH.
Intrarenal angiotensin I conversion at normal and reduced renal blood flow in the dog
Authors: Rosivall L. , Rinder D. F. , Champion J. , Khosla M. C. , Navar L. G. , Oparil S.
Published: December 2017

Intrarenal conversion of angiotensin I (ANG I) to angiotensin II (ANG II) under conditions of normal and reduced renal blood flow (RBF) elicited by constriction of the renal artery was examined in pentobarbital-anesthetized dogs. In eight animals, tracer doses of 125I-ANG I (5-12 pmol) were injected into the renal artery and 125I-ANG I, 125I-ANG II, and 125I-labeled metabolites were measured in renal venous effluent by high-voltage paper electrophoresis. The mean conversion of ANG I to ANG II during a single passage through the kidney was 21.8 +/- 2.1% at control RBF. When RBF was decreased by 25 and 53%, percent ANG I conversion was not altered significantly. In six dogs percent conversion of 125I-[Sar1, Ile5]ANG I, an ANG I analogue refractory to hydrolysis by aminopeptidases, was 18.1 +/- 1.7% at control RBF and did not change significantly when the RBF was reduced by 55%. Although there were severalfold increases in renal renin secretion rate and net ANG I generation rate during reduced RBF, net renal ANG II formation rate did not change significantly. These data indicate that there is substantial conversion of ANG I in a single passage through the dog kidney and that intrarenal ANG I conversion is independent of RBF even under conditions in which renin secretion rate and ANG I generation rate are increased severalfold.
Suppression of distal urinary acidification after recovery from chronic hypocapnia
Authors: Batlle D. C. , Itsarayoungyuen K. , Downer M. , Foley R. , Arruda J. A. , Kurtzman N. A.
Published: December 2017

This study examined urinary acidification shortly after recovery from chronic hypocapnia induced by hypoxemia. Distal acidification was evaluated by measuring the urinary PCO2 and urine-blood PCO2 difference (U-B PCO2) when blood PCO2 had returned to normal. In posthypocapnic rats, maximal alkalinization of the urine by acute sodium bicarbonate loading failed to increase urine PCO2 and U-B PCO2 to the level of posthypoxemic control rats and normal control rats with comparable blood pH and urine bicarbonate concentration. To test the hypothesis that decreased distal hydrogen ion secretion in posthypocapnic rats resulted from intracellular alkalosis secondary to protracted hypocarbia, posthypocapnic rats were exposed to hypercapnia of brief duration (30 min) and prolonged duration (120 min) in an attempt to restore distal acidification to normal. In posthypocapnic rats, hypercapnia of brief duration was associated with a significant increase in urine PCO2 and a fall in urine pH. Prolonged hypercapnia resulted in a marked increase in urine PCO2 and a further fall in urine pH. At any urinary bicarbonate concentration, however, the urine PCO2 and U-B PCO2 posthypocapnic rats exposed to hypercapnia were still significantly lower than in normal control rats identically subjected to prolonged hypercapnia and with comparable blood PCO2 and blood pH. Our findings indicate that distal acidification after abrupt recovery from chronic hypocapnia is decreased as if the kidneys were still under the influence of sustained hypocapnia. These findings could not be ascribed to extracellular alkalemia but could be explained by postulating that decreased urinary acidification resulted from persistence of cell alkalinity secondary to the accumulation of non-CO2 buffers generated during protracted hypocarbia. Alternatively, factors other than cell pH could mediate the adaptive decrease in distal hydrogen ion secretion of posthypocapnic rats.
Transepithelial voltage changes during prostatic secretion in the dog
Authors: Smith E. R. , Miller T. B. , Pebler R. F.
Published: December 2017

To define the nature of Na+, K+, and Cl- secretion by the dog prostate, the electrical potential difference between fluid in the prostatic urethra and venous blood was recorded during secretion provoked in pentobarbital-anesthetized dogs by electrically stimulating the hypogastric nerves or by administering pilocarpine intravenously. The resultant prostatic fluid samples as well as plasma samples taken before and/or after secretion were analyzed for these electrolytes. During secretion provoked by either means the transepithelial electrical potential difference, which was essentially zero at rest, became lumen negative, the maximum change (which was related to gland size) being about 4 mV. The time courses of both the potential change and the secretion of fluid were very similar. The Na+ concentration in both nerve- and pilocarpine-induced prostatic fluid was equal to that in plasma, whereas the K+ and Cl- concentrations were higher than in plasma. It is concluded that Na+ may move passively from plasma into prostatic fluid, perhaps via the paracellular route, but the movement of K+ and Cl- probably involves active transcellular transport.
Flow dependence of proximal tubular bicarbonate absorption
Authors: Alpern R. J. , Cogan M. G. , Rector F. C.
Published: December 2017

Rat proximal convoluted tubules were microperfused in vivo to examine the effect of flow rate on bicarbonate absorption. When tubules were perfused with 25 mM bicarbonate, increases in perfusion rate from 15 to 33 to 49 nl/min caused bicarbonate absorption to increase from 105 +/- 4 to 176 +/- 8 to 209 +/- 7 pmol X mm-1 X min-1, respectively. Only 15% of this stimulation could be attributed to a flow-induced increase in the measured axial luminal bicarbonate concentration profile. In addition, effects of flow on passive bicarbonate diffusion or convection could not account for the observed stimulation. When tubules were perfused with 58 mM bicarbonate (a concentration previously shown to achieve maximal rates of proton secretion), increasing flow rate from 15 to 49 nl/min did not stimulate bicarbonate absorption. Thus, when examined as a function of mean luminal bicarbonate concentration, increases in flow increased the rate of proton secretion without affecting the maximal rate. The data are most consistent with flow-dependent stimulation of bicarbonate absorption, secondary to flow-dependent changes in luminal bicarbonate concentration, occurring by two mechanisms: 1) flow-dependent increases in the measured axial luminal bicarbonate concentration profile and 2) flow-dependent decreases in radial luminal bicarbonate concentration gradients.
Effects of variations in renal hemodynamics on the time course of renin secretion rate
Authors: Simchon S. , Chien S.
Published: December 2017

The effects of variations in renal hemodynamics on the time course of renin secretion were studied in dogs anesthetized with pentobarbital-chloralose. Hemodynamic changes were induced either locally in kidneys perfused in situ via an extracorporeal circuit (with or without a pump system) or systemically by hemorrhage or nitroprusside infusion. In the autoperfused kidney the reduction of renal perfusion pressure to approximately one-half of the arterial pressure by inflow occlusion caused an increase in renal conductance (renal vasodilation) and an increase in renin secretion rate (RSR). In the pump-perfused kidney, a step increase in renal blood flow (RBF) caused renal vasoconstriction and a decrease in RSR; a step decrease in RBF caused renal vasodilation and an increase in RSR. Following step changes in RBF, the time constant of the alterations of renal conductance was 56.5 s, and the time constant of the RSR responses was 80.1 s. The total time required to reach a steady state for RSR lagged behind that for renal conductance by approximately 5 min. These differences reflect the time needed for the kidney to release renin in response to changes in renal vascular caliber. The results suggest that renin release occurs in response to the autoregulatory dilation of the renal arterioles. When systemic hypotension was induced by nitroprusside infusion, RSR also increased together with the renal conductance. Following hemorrhage, however, RSR increased despite a decrease in renal conductance, reflecting the role of neurohumoral factors in causing renin release in this case. The comparison of renin secretion following different types of hemodynamic alterations serves to elucidate the mechanisms of renin secretion.
Thyroparathyroidectomy exaggerates calciuric action of ammonium chloride in rats
Authors: Goulding A. , Campbell D. R.
Published: December 2017

The effects of chronic ammonium chloride (NH4Cl) administration on urinary calcium, urinary hydroxyproline, and calcium and phosphate balances were studied in intact and thyroparathyroidectomized (TPTX) rats. NH4Cl (2 g/100 g diet) was administered for 16 days to growing rats consuming a low calcium (0.1% Ca) diet. NH4Cl increased urinary calcium and hydroxyproline. NH4Cl caused greater urinary calcium loss in TPTX than in intact rats, but hydroxyproline excretion in these groups was similar. Compensatory increases in net alimentary absorption of calcium and phosphate occurred in intact but not in TPTX rats. Urinary cAMP was depressed by thyroparathyroidectomy but was unaffected by NH4Cl. It is concluded that NH4Cl depresses renal tubular reabsorption of calcium and increases bone resorption in the presence and absence of the thyroid and parathyroid glands. However, our results suggest that parathyroid hormone plays an important calcium-sparing role, while calcitonin may act to limit the rate of bone resorption, in intact rats during chronic administration of NH4Cl.
Effect of thyroxine administration on phosphate transport across renal cortical brush border membrane
Authors: Espinosa R. E. , Keller M. J. , Yusufi A. N. , Dousa T. P.
Published: December 2017

Previous studies indicate that in hyperthyroid states the renal tubular reabsorption of phosphate is enhanced. To determine the cellular basis of this phenomenon, we investigated the effect of L-thyroxine (T4) administration on Pi transport across brush border membrane vesicles (BBMV) from rat renal cortex. Rats were thyroparathyroidectomized, fed a diet containing 1.2% phosphate, and treated intraperitoneally for 6 days with 200 micrograms T4 X 100 g body wt-1 X day-1. At the end of the treatment period, the rats had a significantly (+ delta 25%) elevated plasma Pi and a slightly decreased plasma Ca compared with controls. The renal clearance of Pi was not different between the two groups. Na+ gradient-dependent uptake of 32Pi by BBMV from renal cortex was significantly enhanced in T4-treated rats. BBMV uptake of 32Pi in the absence of Na+ -gradient as well as Na+ gradient-dependent uptake of D-[3H]glucose and L-[3H]proline did not differ between BBMV from T4-treated and control rats. Kinetic analysis showed that the Na+ gradient-dependent 32Pi transport system in BBMV from T4-treated rats had a significantly increased Vmax compared with controls (5.2 +/- 0.4 vs. 4.1 +/- 0.4 nmol Pi X 30 s-1 X mg protein-1) and also a slightly higher affinity for Pi (apparent Km in controls, 95 +/- 9; in T4-treated, 78 +/- 8 microM). Gluconeogenesis in cortical slices was not significantly different between T4-treated rats and controls. Specific activities of alkaline phosphatase and gamma-glutamyltransferase were significantly lower in BBMV from the T4-treated group compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
PTH-like glucagon stimulation of Ca and Mg reabsorption in Henle's loop of the rat
Authors: Bailly C. , Roinel N. , Amiel C.
Published: December 2017

The effects of glucagon and PTH on renal tubular electrolyte handling were studied in anesthetized, thyroparathyroidectomized Brattleboro rats infused with somatostatin. Fractional excretion of Ca and Mg was significantly lower during infusion of both hormones. Micropunctures of same nephrons localized the bulk of the increase in reabsorption in Henle's loop, where both hormones significantly enhanced the reabsorptive capacities for Ca, Mg, and K. Beyond the early distal tubule, Ca and Mg reabsorption was significantly greater during glucagon infusion and Ca reabsorption was significantly greater during PTH infusion. Cyclic adenosine monophosphate at a plasma concentration of 10(-6) M did not reproduce the effects of either glucagon or PTH. These results are similar to the findings reported for the effects of ADH and calcitonin on Ca, Mg, and K tubular handling, but different as far as Na and Cl are concerned, since their loop reabsorption was not significantly altered by glucagon and PTH. The data obtained here for glucagon and PTH, together with those for ADH and calcitonin, support the hypothesis that these four hormones exert similar effects in the thick ascending limb.
ADH-like effects of calcitonin on electrolyte transport by Henle's loop of rat kidney
Authors: Elalouf J. M. , Roinel N. , de Rouffignac C.
Published: December 2017

The effects of physiological doses of human calcitonin (HCT) on renal excretion and tubular transport of water and electrolytes were investigated in hormone-deprived rats, i.e., homozygous DI Brattleboro rats with reduced levels of circulating glucagon, parathyroid hormone, and thyrocalcitonin, as these hormones are believed, together with ADH, to stimulate the same cells of the thick ascending limb. The experimental design was similar to the one used in a preceding study aimed at determining the effects of ADH in hormone-deprived rats [C. de Rouffignac et al. Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F156-F164, 1983]. In the present experiments, HCT consistently increased the reabsorption of Mg, Ca, and K and, to a lesser extent, Na and Cl in the loop of Henle, but phosphate transport did not rise. The urinary excretion rate of Mg and Ca fell significantly. These data are very similar to the findings obtained with ADH on hormone-deprived rats. It is concluded that, in vivo, administration of HCT 1) stimulates reabsorption of Na, Cl, Mg, Ca, and K by the thick ascending limb, and 2) consistently enhances Mg and Ca reabsorption by the whole kidney by enhancing reabsorption in the loop of Henle. The similarity of the physiological responses elicited by ADH and calcitonin on the thick ascending limb supports the hypothesis of multiple hormonal control of electrolyte transport by the thick ascending limb.
Extravascular CBG-like sites in rat kidney and mineralocorticoid receptor specificity
Authors: Stephenson G. , Krozowski Z. , Funder J. W.
Published: December 2017

To determine the intrarenal distribution of extravascular corticosteroid-binding globulin- (CBG) like sites, we measured the specific binding of [3H]corticosterone to supernatants prepared from papilla-inner medulla, outer medulla, and cortex from adrenalectomized rats. Renal papilla-inner medulla of exhaustively perfused kidneys contained 8-20 times higher concentrations of such sites than cortex or outer medulla. The ontogeny and steroid specificities of such sites were identical to those of plasma CBG; their molar concentration in the inner medulla-papilla was 4 times that of plasma CBG, consistent with local accumulation of CBG. Cytosols from all three zones bound [3H]aldosterone in the presence of RU-26988, a highly specific synthetic glucocorticoid, with high affinity (Kd 4 degrees C, 0.3-0.4 X 10(-9) M) and limited capacity (papilla-inner medulla, 23-34; outer medulla, 15-16; cortex, 12-17 fmol/mg). In papilla-inner medulla the apparent specificity of such [3H]aldosterone binding sites was aldosterone greater than corticosterone greater than dexamethasone, in contrast to aldosterone = corticosterone greater than dexamethasone in outer medulla and cortex. We propose that extravascular CBG confers mineralocorticoid specificity on the papilla-inner medulla [3H]aldosterone binding sites. In addition, given the higher levels of extravascular than intravascular CBG and the recurrent vascular architecture of the renal medulla-papilla, a countercurrent exchange model is proposed for renewable sequestration of corticosterone in the region.
Further studies of organic base secretion by rabbit proximal tubules
Authors: McKinney T. D.
Published: December 2017

The aim of the present studies was to further characterize the mechanisms responsible for the secretion of the organic base procainamide by measuring [3H] procainamide transport in superficial (SF) and juxtamedullary (JM) S2 segments of rabbit proximal tubules perfused in vitro. When perfusate pH was changed from 7.4 to 6.2, procainamide secretion increased by 227% in SF and by 159% in JM tubules. In the presence of ouabain the acidic perfusate caused only a minimal increase in procainamide secretion. When the perfusate pH was increased, procainamide secretion was reduced. Acetazolamide, 10(-5) M in the bath, reduced procainamide secretion in both SF and JM tubules. In SF tubules amiloride, 10(-4) M in the perfusate, inhibited procainamide secretion, whereas nonradioactive procainamide, quinidine, and cimetidine did not. When ambient sodium was reduced to 10 mM, the rate of procainamide secretion was low and was not affected by amiloride in the perfusate or acetazolamide in the bath. Amiloride in the bath caused a dose-related inhibition of procainamide secretion. The rate of procainamide secretion by cortical collecting tubules was very low and was not affected by acetazolamide. The mechanisms of renal organic base secretion are complex. Some of the present data are consistent with a mechanism involving organic base-proton exchange across the apical cell membrane. However, other data are not consistent with this being the major mechanism involved.
Inhibition by bradykinin of renal adrenergic effects in anesthetized rats
Authors: Inokuchi K. , Malik K. U.
Published: December 2017

We studied the contribution of prostaglandins to the actions of bradykinin at the renal vascular adrenergic neuroeffector junction by examining the effect of the peptide on the decrease in renal blood flow elicited by renal nerve stimulation and injected norepinephrine in pentobarbital-anesthetized rats with or without pretreatment with the cyclooxygenase inhibitors sodium meclofenamate or indomethacin. Infusion of bradykinin, 10 ng X kg-1 X min-1, into the renal artery reduced both the basal and the rise in renal vascular resistance produced by nerve stimulation or norepinephrine. The prostaglandin precursor arachidonic acid, 5 micrograms X kg-1 X min-1, infused into the renal artery, also reduced renal vascular resistance and the vasoconstrictor response elicited by either adrenergic stimulus. In animals pretreated with either sodium meclofenamate or indomethacin, the effect of arachidonic acid, but not that of bradykinin, to produce renal vasodilation and to attenuate adrenergically induced renal vasoconstriction was abolished. These data suggest that bradykinin produces renal vasodilation and inhibits the renal vasoconstrictor effect of adrenergic stimuli in the rat kidney in vivo by a mechanism unrelated to prostaglandin synthesis.
Subcellular sites of insulin hydrolysis in renal proximal tubules
Authors: Hjelle J. T. , Oparil S. , Peterson D. R.
Published: December 2017

The subcellular sites of insulin degradation as measured by trichloroacetic acid precipitation were defined for rabbit renal proximal tubule cells. Fractionation in linear sucrose gradients of the postnuclear supernates prepared from isolated proximal tubule segments revealed three pools of insulin hydrolytic activity. Insulin hydrolytic activity assayed at pH 3.5 distributed in the gradients in a manner nearly identical to the activity of the lysosomal enzymes, N-acetyl-beta-glucosaminidase and alpha-mannosidase. At pH 7.4 the insulin-degrading activity distributed in a bimodal fashion with the major component following the cytosolic enzyme, phosphoglucomutase, and the minor component nearly identically overlapping with the activity of the inner mitochondrial enzyme, cytochrome oxidase. Upon microperfusion of 125I-insulin through proximal straight nephron segments, metabolites of the hormone were not observed in the collected perfusates for six of eight experiments. Average values for percent intact insulin in the original and collected perfusates showed no significant difference. These data suggest that three potential sites for insulin hydrolysis are present in proximal tubule cells, including lysosomes, the cytosol, and mitochondria. The results do not support the concept of degradation occurring at the brush border or contraluminal membranes.
Resetting of tubuloglomerular feedback: evidence for a humoral factor in tubular fluid
Authors: Haberle D. A. , Davis J. M.
Published: December 2017

Experiments were performed on chronically salt-loaded rats to determine whether resetting of tubuloglomerular feedback is caused by changes in the sensitivity of the juxtaglomerular apparatus itself or by changes of tubular fluid composition. The feedback response was quantified in both salt-loaded and salt-deplete rats by measuring early proximal flow rate (EPF) during loop perfusion at 40, 10, and 0 nl/min using tubular fluid harvested from both groups and with Ringer solution. In salt-loaded rats endogenous tubular fluid produced only a small feedback response (EPF40-0 = 1.9 +/- 1.5 nl/min), whereas exogenous tubular fluid from salt-deplete rats or Ringer solution produced normal feedback responses (EPF40-0 = 15.4 +/- 2.0 and 10.6 +/- 1.7 nl/min, respectively). In salt-deplete rats, endogenous tubular fluid and Ringer solution produced feedback responses of similar magnitude (EPF40-0 = 14.2 +/- 1.8 and 13.0 +/- 2.0 nl/min, respectively) but exogenous tubular fluid from salt-loaded rats elicited only a small feedback response (EPF40-0 = 1.5 +/- 1.6 nl/min), indistinguishable from that seen in salt-loaded rats with endogenous tubular fluid. It is concluded that an inhibitory factor in the tubular fluid of chronically salt-loaded rats causes a reduction in tubuloglomerular feedback response.
Effect of acute thyroparathyroidectomy on nephron acidification
Authors: Bengele H. H. , McNamara E. R. , Alexander E. A.
Published: December 2017

The effect of the absence of parathyroid hormone on nephron acidification was determined in rats after acute thyroparathyroidectomy (TPTX). Tubular fluid samples were obtained from the superficial late proximal tubule (LPT), the early distal tubule ( EDT ), and along the inner medullary collecting duct (IMCD), and the results were compared with those obtained from control rats. In the LPT after TPTX, pH was lower, 6.66 +/- 0.01 vs. 6.73 +/- 0.01, and ammonium and net acid delivery were increased significantly. In the EDT no differences in pH, bicarbonate, or net acid were found between groups, whereas ammonium and acid phosphate were significantly different. Along the IMCD in control rats, pH decreased from 6.58 to 5.21 and the addition of about 430 nmol/min of net acid was observed. After TPTX more net acid entered the duct and pH was lower, 5.66, but did not change; neither did the amount of bicarbonate, ammonium, acid phosphate, or net acid change significantly along the duct. Net acid excretion was not different, however, among groups. These results demonstrate that TPTX markedly affects nephron acidification, increasing net acid along the proximal tubule. In contrast to that in control rats, however, net acidification is completed prior to the IMCD. We conclude that the acute absence of parathyroid hormone may significantly affect local nephron acidification but does not alter acid excretion.