bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of a direct effect of atrial natriuretic factor in the rabbit proximal tubule
Authors: Baum M. , Toto R. D.
Published: December 2017

Whole animal clearance studies and in vitro microperfusion studies were performed to examine the effect of atrial natriuretic factor (ANF) on the rabbit proximal tubule. Infusion of ANF into rabbits resulted in an increase in glomerular filtration rate and a natriuresis and diuresis. To determine whether ANF has a direct proximal tubule effect to account for part of the observed natriuresis, proximal convoluted tubules (PCT) and proximal straight tubules (PST) were perfused in vitro. Addition of 10(-9) M ANF, a concentration recently measured in vivo during volume expansion, to the bathing solution of PCT caused no significant change in volume absorption. Addition of a pharmacological concentration of ANF (10(-7) M) to either the bathing solution or the luminal perfusate of PCT resulted in no change in volume absorption. When added to the bathing solution of PST, 10(-7) M ANF did not have an effect on volume absorption. ANF did not affect the transepithelial potential difference in any protocol. In conclusion, these data show that ANF does not affect transport directly in the proximal tubule.
Filtration by superficial and deep glomeruli of normovolemic and volume-depleted rats
Authors: Pinnick R. V. , Savin V. J.
Published: December 2017

We measured glomerular ultrafiltration coefficient (Kf) of isolated superficial (S) and deep (D) glomeruli of normovolemic and volume-depleted rats. Filtration was induced in vitro, and Kf was calculated from the maximum rate of change in glomerular size. Basement membrane area (A) for each glomerulus was estimated from morphometric analyses, and glomerular capillary hydraulic conductivity (Lp) was calculated by the formula Lp = Kf/A. Kf of S and D glomeruli of normovolemic rats were 2.98 +/- 0.98 and 4.25 +/- 0.07 nl . min-1 . mmHg-1, respectively. In hypovolemic rats, Kf of S glomeruli fell by approximately 50% to 1.52 +/- 0.14 nl . min-1 . mmHg-1 (P less than 0.001), whereas Kf of D glomeruli remained unchanged at 4.28 +/- 0.10 nl . min-1 . mmHg-1. Lp, calculated using the peripheral capillary area, averaged 1.98 +/- 0.09 and 1.98 +/- 0.06 microliter . min-1 . mmHg-1 . cm-2 in S and D glomeruli of normovolemic rats and 1.89 +/- 0.11 microliter . min-1 . mmHg-1 . cm-2 in D glomeruli of hypovolemic rats. Lp of S glomeruli of volume-depleted rats (0.90 +/- 0.03 microliter . min-1 . mmHg-1 . cm-2) was lower than in any of the other three samples. Mild hypovolemia causes the Kf of S glomeruli to decline, whereas Kf of D glomeruli remains constant. The decrease in Kf occurs without an alteration in capillary area and is most likely due to a decrease in Lp.
Role of the vasoconstrictor and antidiuretic activities of vasopressin in inhibition of renin secretion in conscious dogs
Authors: Schwartz J. , Reid I. A.
Published: December 2017

The nature of the activity of vasopressin that is responsible for the inhibition of renin secretion was studied in normally hydrated conscious dogs using intravenous infusions of vasopressin and analogues of vasopressin with selective antidiuretic and vasoconstrictor activity. Vasopressin (1.0 ng . kg-1 . min-1) increased mean arterial pressure (MAP) from 106 +/- 2 to 115 +/- 3 mmHg (P less than 0.05) and decreased heart rate (HR) from 81 +/- 6 to 56 +/- 5 beats/min (P less than 0.001). Plasma renin activity (PRA) decreased from 4.4 +/- 1.1 to 2.4 +/- 0.8 ng . ml-1 . 3 h-1 (P less than 0.05). A specific antagonist of the vasoconstrictor activity of vasopressin, d(CH2)5MeTyrAVP (10 micrograms/kg), completely blocked the cardiovascular and renin responses to vasopressin. A selective vasoconstrictor agonist, 2-phenylalanine-8-ornithine oxytocin (1.0 ng . kg-1 . min-1), increased MAP from 112 +/- 4 to 128 +/- 6 mmHg (P less than 0.001) and decreased HR from 69 +/- 3 to 47 +/- 4 beats/min (P less than 0.001). PRA decreased from 5.5 +/- 1.1 to 2.7 +/- 0.2 ng . ml-1 X 3 h-1 (P less than 0.001). In contrast, a selective antidiuretic agonist, 1-deamino-8-D-arginine vasopressin (1.0 ng . kg-1 . min-1) did not alter PRA, MAP, or HR. These results demonstrate that the acute inhibition of renin secretion by vasopressin in normally hydrated conscious dogs is due to vasoconstrictor rather than antidiuretic activity.
Extrinsic innervation of the rat kidney: a retrograde tracing study
Authors: Gattone V. H. , Marfurt C. F. , Dallie S.
Published: December 2017

To determine the exact modalities involved in the innervation of the kidney, the present study used a nerve-tracing method with horseradish peroxidase-wheat germ agglutinin (HRP-WGA) as the tracer. Multiple injections of HRP-WGA were made in each of the left kidneys of 12 rats while another four had the HRP-WGA either dripped onto their intact renal mesothelial surface or injected intravascularly. After retrograde transport of the tracer to neurons of origin (i.e., 72-h survival), the rats were briefly perfusion fixed, tissue was removed, and cryostat sections were cut. The free-floating sections were reacted by the tetramethylbenzidine technique. Retrogradely labeled neurons were found in the celiac, bilateral inferior vagal (nodosal), and ipsilateral dorsal root (90% in T12-L1 DRG) ganglia. More labeled neurons were present in the combined vagal ganglia than in the combined DRG within each animal. This labeling was specific compared with the controls (HRP-WGA uptake via intraperitoneal or vascular routes). The celiac ganglion had many labeled neurons; however, no labeled neurons were seen in the dorsal motor nucleus of the vagus, nucleus solitarius, nucleus ambiguus, or any other brain stem structure after renal injections of HRP-WGA. This study has determined that the sympathetic nervous system (celiac ganglion) provides the only renal autonomic efferent (motor) innervation, and the nodosal (inferior vagal) ganglia appear to provide more renal sensory innervation than do the dorsal root ganglia.
Measurement of intracellular pH with microelectrodes in rat kidney in vivo
Authors: Henderson R. M. , Bell P. B. , Cohen R. D. , Browning C. , Iles R. A.
Published: December 2017

The construction of two types of double-barreled microelectrodes of sufficiently small tip size to record cytosolic pH (pHc) in renal tubular epithelial cells is described. Mean pHc in control anesthetized rats was 7.10 and mean basolateral membrane potential (Em) was -51.8 mV. These results suggest that hydrogen ions are actively extruded from either or both poles of the proximal tubular cell but that bicarbonate exit across the basolateral membrane is passive. In animals treated with acetazolamide, pHc was significantly elevated (mean 7.35) but Em was unchanged, suggesting that proton extrusion continues but that the rate of reaction of OH- with CO2 is diminished due to carbonic anhydrase inhibition. A pH higher than that of arterial blood was obtained from sites presumed to be in the interstitium. The evidence for the various assignments of microelectrode tip position is discussed.
Parathyroid hormone inhibition of Na+-H+ antiporter activity in a cultured renal cell line
Authors: Pollock A. S. , Warnock D. G. , Strewler G. J.
Published: December 2017

The renal effects of parathyroid hormone (PTH) include a decreased rate of acidification by the proximal tubule. To determine whether this effect represented a PTH action on the Na+-H+ antiporter, we investigated the effect of PTH on the established opossum kidney (OK) cell line. This cell line retains several features characteristic of proximal tubule cells, including an amiloride-sensitive Na+-H+ antiporter and high-affinity PTH receptors with a coupled cAMP response. We measured steady-state intracellular pH and amiloride-sensitive 22Na+ uptake as a reflection of the activity of the Na+-H+ antiporter. Under bicarbonate and CO2-free conditions, the steady-state intracellular pH of OK cell cultures was modified by altering the rate of Na+-H+ exchange. When Na+-H+ exchange was inhibited by amiloride, intracellular pH fell. Conversely, augmenting antiporter activity by addition of monensin, a Na+-H+ exchange ionophore, raised intracellular pH. PTH (2.5 X 10(-8) M) lowered intracellular pH by up to 0.17 pH units, and half of the maximum PTH effect was present at a concentration of 10(-12) M. This effect was not seen in the presence of amiloride or in the absence of sodium, suggesting that a functional Na+-H+ antiporter is necessary for its expression. The decrease in intracellular pH was reproduced by forskolin and 8-bromo-cAMP, suggesting that this is a cAMP-mediated effect. PTH, forskolin, and 8-bromo-cAMP also decreased the amiloride-sensitive component of 22Na+ uptake in OK cells by up to 64%, whereas the amiloride-insensitive component was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of renal denervation on renal responses to hypoxemia in fetal lambs
Authors: Robillard J. E. , Nakamura K. T. , DiBona G. F.
Published: December 2017

The role of renal nerves in mediating renal hemodynamics and renal function during normal physiological conditions and following moderate hypoxemia was studied in chronically catheterized fetal lambs (125-141 days of gestation) following unilateral renal denervation. Base-line values for renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow rate (UFR), urinary electrolyte (Na+, K+, and Cl-) excretion rate, and urine osmolality (Uosm) were similar in both intact and denervated kidneys. Hypoxemia was associated with a significant rise in mean arterial blood pressure and a significant decrease in heart rate. Hypoxemia produced a similar decrease in GFR and similar increases in urinary Na+ and Cl- excretion rates in both intact and denervated kidneys. However, the effect of hypoxemia on renal hemodynamics differed between intact and denervated kidneys. Hypoxemia produced a continuous and progressive decrease in RBF and increase in RVR in the intact kidney. On the other hand, renal denervation was associated with an early renal vasodilation and attenuated the reduction in RBF and the rise in RVR during hypoxemia; this early renal vasodilation was blunted following prostaglandin synthesis inhibition. Taken together, these results suggest that fetal renal denervation is not associated with significant changes in renal hemodynamics or renal function during normal physiological conditions but that renal denervation partially inhibited the renal vasoconstriction associated with fetal hypoxemia. Finally, it was found that endogenous prostaglandins counteract the renal vasoconstriction associated with fetal hypoxemia.
Effect of renal perfusion pressure on sodium reabsorption from proximal tubules of superficial and deep nephrons
Authors: Haas J. A. , Granger J. P. , Knox F. G.
Published: December 2017

Previous studies in rats have demonstrated that superficial proximal tubule sodium reabsorption does not change in response to alterations in renal perfusion pressure (RPP). The first objective of the present study was to estimate sodium reabsorption in response to acute changes in RPP utilizing fractional lithium reabsorption (FRLi) as an index of fractional sodium reabsorption (FRNa) by the proximal tubule of the kidney as a whole. FRLi decreased in response to increases in RPP, suggesting that sodium reabsorption by the proximal tubule of some nephron population is decreased. Therefore, the second objective of the present study was to test the hypothesis that superficial and deep proximal tubules respond differently to changes in RPP by comparing proximal tubule sodium reabsorption from both nephron populations. In response to an acute change in RPP from 114 +/- 4 to 138 +/- 5 mmHg, FRNa by the proximal tubule and descending limb of Henle's loop in deep nephrons decreased from 71.3 +/- 2.3 to 55.8 +/- 5.6%, but FRNa by the superficial late proximal tubule was not changed: (44.3 +/- 4.8 to 45.1 +/- 3.9%). The urinary fractional reabsorption of sodium decreased from 96.7 +/- 0.6 to 94.5 +/- 0.5%. In summary, these studies demonstrate that increases in RPP have no effect on sodium reabsorption by the proximal tubule of superficial nephrons. In contrast, sodium delivery to the point of micropuncture in the descending limb of Henle's loop of deep nephrons was increased, suggesting inhibition of sodium reabsorption by proximal tubules of deep nephrons in response to increases in RPP.
Evidence that prostaglandin E2 stimulates chloride secretion in cultured A6 renal epithelial cells
Authors: Keeler R. , Wong N. L.
Published: December 2017

The effects of prostaglandin E2 (PGE2) on the transport of sodium and chloride were studied in cultured A6 renal epithelial cells. PGE2 on the basolateral but not the apical surface increased transmonolayer short-circuit current (Isc) and conductance. These changes could not be inhibited with amiloride or furosemide in the apical medium. Flux measurements showed that although Isc and net flux of sodium were equal in unstimulated cells, after addition of PGE2 the current increased with no corresponding changes in bidirectional or net flux of sodium. Immersing the cells in sodium-free or chloride-free media inhibited the effects of PGE2. Measurements of the simultaneous fluxes of sodium and chloride showed that after PGE2 was added there was a net flux of chloride from the basal to the apical side (secretion) that was equal to the change in Isc. The effects of PGE2 were inhibited by furosemide in the basal medium. We conclude that PGE2 stimulates a process of chloride secretion in A6 cells.
Prostaglandins may mediate chloride concentration gradient across domes formed by MDCK1 cells
Authors: Lifschitz M. D.
Published: December 2017

The MDCK1 and LLC-PK1 cell lines have been used to characterize transepithelial transport in isolated culture. Both can be maintained in continuous culture and form domes that represent fluid actively transported from luminal to contraluminal surface. Fluid in domes from LLC-PK1 cells was isotonic with the culture medium and no Cl gradient between domes and medium was present. Fluid from domes formed by MDCK1 cells was also isotonic with respect to Na and K but there was a persistent Cl concentration gradient. To evaluate prostaglandin (PG) production by these cell lines, the culture medium was analyzed for PGE. LLC-PK1 cells released no measurable PGE; MDCK1 cells regularly released PGE both during basal conditions and after augmentation of PG synthesis by a high Ca concentration in the medium. Qualitatively similar results had previously been found with these cell lines when PG synthesis was augmented with addition of arachidonic acid or Ca ionophore A23187, and PGE or 6-keto-prostaglandin F1 alpha was measured in the medium. To evaluate whether PGs might be responsible for the Cl gradient across MDCK1 cells, indomethacin or meclofenamate was added. There was a marked decrease in the Cl gradient with either agent at 5 h. To evaluate the possibility that PGE2 or PGI2 plays a role in maintaining this Cl gradient, further studies were done in which indomethacin was added to the culture medium to block endogenous PG synthesis, and exogenous PGE2 or PGI2 was added. Although addition of PGE2 was without effect, addition of PGI2 to indomethacin-treated cells maintained the Cl gradient for at least 5 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of graded changes in reflex renal nerve activity on renal function
Authors: Beers E. T. , Carroll R. G. , Young D. B. , Guyton A. C.
Published: December 2017

The effects of reflexly produced graded increases in renal nerve activity on excretion of sodium and potassium, urinary flow, glomerular filtration rate (GFR), renal plasma flow (RPF), renin release, and renal venous norepinephrine (NE) overflow were examined in anesthetized dogs. Renal nerve activity was increased by carotid artery occlusion while renal perfusion pressure was held constant. Linear correlation was determined by plotting the percent change from control for each dependent variable vs. the percent change in mean renal nerve activity (MRNA). The percent changes from control for sodium excretion and urinary flow were negatively correlated with percent change from control in MRNA (P less than 0.01), and the percent change from control for renin release was positively correlated with percent change from control in MRNA (P less than 0.05). NE overflow was observed to increase as renal nerve activity increased. These results indicate that physiologically elicited increases in MRNA from 10 to greater than 100% are significantly correlated with changes in sodium excretion, urine flow, and renin release with little or no measurable change in GFR, RPF, or potassium excretion.
Human renal response to meat meal
Authors: Hostetter T. H.
Published: December 2017

Glomerular filtration rate (GFR) increases after a meat meal in several species. The mechanism of this phenomenon is unknown and the excretory and metabolic responses largely unexplored. We examined in humans the nature of the hemodynamic response to a meat meal, the role of salt and water load in this response, and the associated renal excretory responses. Ten normal volunteers were studied after eating an average of 3.5 g/kg body wt of lean cooked beef steak and, on a separate day, after ingesting an amount of sodium and water equivalent to that in the steak. Average GFR increased by 28% for the entire 3 h after the meat meal compared with the same time period after the control salt solution (90 +/- 8 vs. 114 +/- 6 ml X min-1 X 1.73 M-2, mean +/- SE, P less than 0.05) and by 15% compared with the base-line periods, although this difference was not of statistical significance. However, not all subjects demonstrated an increase, and in those eight who did the degree was variable from 5 to 46% for the 3-h mean above the basal value. During the hour of peak GFR, the increment was associated with a nearly proportional increase in renal plasma flow and renal blood flow (all P less than 0.05). The increase in renal blood flow was entirely due to a significant fall in renal vascular resistance. The vasodilation was not accompanied by any change in prostaglandin E excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal mitochondrial glutamine metabolism during K+ depletion
Authors: Sastrasinh S. , Sastrasinh M.
Published: December 2017

We studied changes in renal mitochondrial glutamine metabolism during the development of and recovery from K+ depletion in rats. Significant increase in mitochondrial NH3 production was noted after 3 days of K+-free diet. Ammoniagenesis in K+-depleted animals reached maximal level within 2 wk of K+ deprivation when there was 64% increase in NH3 production. In contrast to the pattern of changes in mitochondrial ammoniagenesis, phosphate-dependent glutaminase (PDG) activity increased within the first 48 h of K+ deprivation, before there was any increase in NH3 production, and did not plateau even after 2 wk of K+-free diet. The disparity between NH3 production and PDG activity cannot be explained by the difference in matrix glutamate level, thus raising the possibility that mitochondrial glutamine entry may be a rate-limiting step for ammoniagenesis during K+ depletion. Recovery from K+ depletion was studied in animals prefed with K+-free diet for 2 wk prior to the initiation of K+-supplemented diet. Muscle K+ content of K+-depleted animals returned to normal after 1 wk of K+ replacement. Mitochondrial NH3 production decreased concomitantly with the attenuation in K+ deficit but did not reach the base-line value even after K+ deficit was completely corrected. Additional experiments with isolated cortical tubules also showed persistent increase in NH3 production after the correction of K+ deficit. Thus, unlike earlier studies in rats during the recovery from metabolic acidosis, which showed only increased ammoniagenesis in isolated mitochondria but not in cortical slices, animals recovered from K+ depletion demonstrated augmented NH3 production both in isolated mitochondria and intact renal tissues.
Dependence of ion fluxes on fluid transport by rat proximal tubule
Authors: Bomsztyk K. , Wright F. S.
Published: December 2017

The effects of changes in transepithelial water flux (Jv) on sodium, chloride, calcium, and potassium transport by the proximal convoluted tubule were examined by applying a microperfusion technique to surface segments in kidneys of anesthetized rats. Perfusion solutions were prepared with ion concentrations similar to those in fluid normally present in the later parts of the proximal tubule. Osmolality of the perfusate was adjusted with mannitol. With no mannitol in the perfusates, net fluid absorption was observed. Addition of increasing amounts of mannitol first reduced Jv to zero and then reversed net fluid flux. At the maximal rates of fluid absorption, net absorption of Na, Cl, Ca, and K was observed. When Jv was reduced to zero, Na, Cl, and Ca absorption were reduced and K entered the lumen. Na, Cl, and Ca secretion occurred in association with the highest rates of net fluid secretion. The lumen-positive transepithelial potential progressively increased as the net fluid flux was reduced to zero and then reversed. The results demonstrate that changes in net water flux can affect Na, Cl, Ca, and K transport by the proximal convoluted tubule of the rat kidney. These changes in net ion fluxes are not entirely accounted for by changes in bulk-phase transepithelial electrochemical gradients.
Calcium channel blockers enhance extrarenal potassium disposal in the rat
Authors: Sugarman A. , Kahn T.
Published: December 2017

The effect of calcium channel blockers on the extrarenal disposition of an acute potassium load was examined in acutely nephrectomized rats infused with KCl (0.75 meq X kg-1 X h-1 for 60 min) alone or in combination with either verapamil or nifedipine. The increment in plasma potassium concentration during the potassium infusion (delta PK) with either verapamil or nifedipine was less than control (P less than 0.05 and 0.01, respectively). Studies were repeated in acutely adrenalectomized rats (ADX) to evaluate whether the changes in plasma potassium were consequent to the enhanced activity of epinephrine and other adrenal hormones. delta PK with ADX was higher than control (P less than 0.01). Verapamil or nifedipine with ADX resulted in a lower delta PK than ADX alone (P less than 0.05). Further studies were then conducted with the selective beta 2-adrenergic blocker butoxamine hydrochloride to rule out enhanced peripheral sympathetic activity of the beta 2-adrenergic system in facilitating the potassium disposal. delta PK with butoxamine was greater than control (P less than 0.01) but not significantly different from ADX. Verapamil or nifedipine in conjunction with butoxamine resulted in a lower delta PK than butoxamine alone (P less than 0.01). Changes in arterial pH and plasma bicarbonate were similar in all groups. In conclusion, during potassium infusion the delta PK is lower in the presence of calcium channel blockers. The alteration in potassium transport produced by calcium channel blockers does not appear to be dependent on adrenal function or peripheral sympathetic activity. Impaired calcium entry into cells may alter potassium transport in the intact animal.
Angiotensin-receptor signaling in cultured vascular smooth muscle cells
Authors: Smith J. B.
Published: December 2017

Functional receptors for angiotensin II (ANG II) are present in smooth muscle cells cultured from rat aorta. These cells are especially suitable for investigating transmembrane signaling events, since ANG II-receptor function is consistently expressed for many population doublings in culture. Cytoplasmic free Ca, measured with quin 2 or fura-2, transiently increases after receptor stimulation. ANG II releases Ca that is sequestered intracellularly, since the removal of extracellular Ca does not prevent the hormone from increasing intracellular free Ca. Angiotensin provokes both polyphosphoinositide hydrolysis and phosphatidate-phosphoinositide synthesis. Purified inositol trisphosphate (IP3) releases Ca from a nonmitochondrial organelle, presumably the sarcoplasmic reticulum or a specialized region therein. IP3 probably opens an intracellular Ca channel by a ligand-binding reaction rather than a metabolic reaction. The accumulation of IP3 in intact cells in response to ANG II seems fast enough to cause Ca mobilization. ANG II increases a fast and a slow component of 45Ca2+ efflux from the intact cells. The rapid stimulation of Ca2+ efflux from the cell via a Na-Ca antiporter probably accounts at least in part for the short duration of the increase in cytoplasmic free Ca elicited by angiotensin. ANG II has no effect on a fast component of 45Ca2+ influx but does increase a slow component of 45Ca2+ influx; that increase would help to sustain the elevation in free Ca and the refilling of the sarcoplasmic reticulum. Additionally, ANG II-receptor stimulation depolarizes the cell membrane and increases the specific activities of the Na-K pump, the Na-H antiporter, the Na-Ca antiporter, and the Na-K-Cl cotransporter. Ca and/or 1,2-diacylglycerol, the lipophilic activator of protein kinase C, which is concomitantly produced along with IP3, may mediate the effects of ANG II on Na and K transport. Investigations of cultured vascular smooth muscle support the inositol-signaling hypothesis of hormone action.
High Ca2+ inhibits AVP-dependent cAMP production in thick ascending limbs of Henle
Authors: Takaichi K. , Uchida S. , Kurokawa K.
Published: December 2017

To further gain insights into the mechanisms underlying impaired urine concentration in hypercalcemia, effects of increasing Ca2+ concentrations in the incubation medium on cAMP production in response to 10(-8) M arginine vasopression (AVP) were examined in thick ascending limbs of Henle (MTAL) and collecting tubules (MCT) dissected from outer medulla of mouse kidney. Increasing Ca2+ in the incubation medium from 1.0 mM to either 2.0 mM or 5.0 mM inhibited AVP-dependent cAMP production in MTAL but not in MCT. This inhibition of AVP-dependent cAMP production by 2.0 mM Ca2+ in MTAL was not reversed by verapamil or diltiazem. Also, Ca2+ ionophore A23187 did not inhibit AVP-dependent cAMP production in MTAL in the presence of 1.0 mM Ca2+. Increasing medium Ca2+ from 1.0 to 5.0 mM inhibited cAMP production in MTAL in response to both glucagon and forskolin by the magnitude comparable to that seen in response to AVP. These results show that high Ca2+ inhibits AVP-dependent cAMP production only in MTAL and not in MCT. In addition, the lack of effects of Ca2+ channel blockers and Ca2+ ionophore suggests that high ambient Ca2+ per se may inhibit AVP-dependent cAMP production in MTAL. The fact that high Ca2+ also suppressed cAMP production in response to glucagon or forskolin suggests that Ca2+ may inhibit AVP-dependent adenylate cyclase at postreceptor site(s), one of which is the catalytic unit of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
Time-dependent attenuation of water flow in antidiuretic hormone-treated toad bladder
Authors: Kachadorian W. A. , Muller J. , Ellis S. J.
Published: December 2017

Toad urinary bladders were subjected to sequential 30-min stimulation with antidiuretic hormone (ADH) followed by 30-min hormone washout over 4 h in the absence of a transmural osmotic gradient. Immediately thereafter, during test stimulation with hormone in the presence of a transmural gradient, transbladder water flow was profoundly inhibited, but intra(luminal)membrane particle aggregates, presumed markers of luminal membrane water permeability, were as numerous as in fully responsive controls. The protocol followed was designed to eliminate any distorting effect of prior water flow on cytoplasmic organization and to equalize, for both experimental and control tissues, the time of aggregate presence in the luminal membrane during final test stimulation. On the assumption that cytoplasmically stored and/or newly synthesized aggregates would be unaffected by the protocol followed, these observations appear to be consistent with the view that bladder refractoriness to prolonged ADH treatment may involve regulation of tissue water permeability at a resistance distal to the luminal membrane.
Prostaglandin blockade impairs denervation diuresis and natriuresis in the rat
Authors: Barber J. D. , Harrington W. W. , Moss N. G. , Gottschalk C. W.
Published: December 2017

Acute unilateral renal denervation of control rats produced an ipsilateral diuresis (5.5 +/- 0.8 to 10.0 +/- 1.0 microliter/min, P less than 0.01) and natriuresis (579 +/- 202 to 2,668 +/- 225 neq/min, P less than 0.01) without a significant change in glomerular filtration rate or effective renal plasma flow. Inhibition of prostaglandin synthesis with indomethacin or meclofenamate (4 mg/kg iv) after acute unilateral denervation eliminated the diuresis (13.3 +/- 1.6 to 5.0 +/- 0.9 microliter/min, P less than 0.01) and attenuated the natriuresis (3,098 +/- 462 to 1,097 +/- 163 neq/min, P less than 0.01). Denervation diuresis and natriuresis were significantly impaired to the same extent when denervation was performed after inhibition of prostaglandin synthesis (3.2 +/- 0.3 to 4.9 +/- 0.4 microliter/min, NS; and 490 +/- 154 to 1,036 +/- 274 neq/min, P less than 0.05 vs. control, respectively). These results indicate that the natriuresis and diuresis seen after acute unilateral denervation in anesthetized rats are highly dependent upon prostaglandins and cannot be initiated or maintained when prostaglandin synthesis is impaired by indomethacin or meclofenamate.
Adenosine alters glomerular filtration control by angiotensin II
Authors: Hall J. E. , Granger J. P.
Published: December 2017

This study was designed to test the hypothesis that high renal levels of adenosine (ADO) may alter glomerular filtration rate (GFR) control by angiotensin II (ANG II). In normal kidneys, ANG II infusion (20 ng X kg-1 X min-1 iv) decreased renal blood flow (RBF) to 61 +/- 3% of control, increased filtration fraction (FF) to 173 +/- 21% of control, and did not change GFR significantly. During intrarenal ADO infusion at a rate of 1.0 mumol/min, ANG II (20 ng X kg-1 X min-1 iv) decreased RBF and GFR to 61 +/- 5 and 64 +/- 6% of control, respectively. After blocking changes in tubuloglomerular feedback by occluding the ureter during mannitol diuresis, ANG II increased stop-flow pressure and postglomerular resistance (RPG) markedly but did not alter preglomerular resistance (RA), suggesting that the direct actions of circulating ANG II are confined primarily to efferent arterioles in the absence of changes in tubuloglomerular feedback. However, during intrarenal ADO infusion and inhibition of tubuloglomerular feedback, ANG II decreased stop-flow ureteral pressure and raised RA and RPG to 213 +/- 27 and 155 +/- 7% of control, respectively, while decreasing RBF to 59 +/- 5% of control. These observations suggest that ADO markedly alters the control of GFR by ANG II, possibly by causing ANG II to constrict preglomerular vessels, an effect that is not apparent in most physiological conditions but which could play a role in lowering GFR when renal ADO and ANG II levels are both elevated, as in severe renal ischemia.
Diurnal potassium excretory cycles in the rat
Authors: Rabinowitz L. , Wydner C. J. , Smith K. M. , Yamauchi H.
Published: December 2017

Diurnal potassium cycles (DPC) were measured in unanesthetized undisturbed rats fed a liquid diet and maintained in a 12-h light-dark environment. A fourfold step increase in diet potassium content increased DPC amplitude without altering phase. After presentation of the high-potassium diet, the initial adaptive increase in excretion occurred within 1.5 h (diet given during dark phase) and within 6 h (diet given during light phase). On a day when food was withheld (no potassium intake), DPC were present but with a lowered amplitude. The amount of potassium excreted on a fasting day exceeded gut and extracellular fluid potassium content and was only modestly increased when rats were previously fed a high-potassium diet. In adrenalectomized rats that received no steroid replacement or received constant infusions of low levels of aldosterone, dexamethasone, or aldosterone plus dexamethasone, potassium balance and DPC were normal. It is concluded that the amplitude of DPC in the rat is determined in part by the availability of potassium from both intracellular and extracellular potassium pools; mechanisms independent of potassium intake can generate the DPC; and the presence or the cyclic secretion of adrenal steroids is not necessary for the generation of DPC in the rat.
Possible role of calcium in parathyroid hormone actions in rabbit renal proximal tubules
Authors: Yanagawa N. , Jo O. D.
Published: December 2017

Using a glucose microassay and in vitro isolated renal tubule perfusion technique, we have studied the actions of parathyroid hormone (PTH) on gluconeogenesis (GNG) and fluid (Jv) and phosphate (Jp) transport rates in isolated rabbit renal proximal tubules. In proximal straight tubules (PST), PTH stimulated GNG and inhibited Jv and Jp. In proximal convoluted tubules (PCT), PTH inhibited Jv but failed to affect GNG and Jp. An increase in Ca concentration, however, stimulated GNG and allowed PTH to inhibit Jp in PCT. Addition of the intracellular Ca antagonists trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) abolished the inhibitory effects of PTH on Jv and Jp in both PCT and PST. In conclusion, these studies suggest that Ca-dependent intracellular pathways may be involved in the actions of PTH in rabbit renal proximal tubules. The altered response to PTH in rabbit PCT may be due to alterations in the response of intracellular Ca to the hormone.
Structural-functional relationships along the distal nephron
Authors: Madsen Kirsten M. , Tisher C. Craig
Published: December 2017

Pages F1–F15: Kirsten M. Madsen and C. Craig Tisher. “Structural-functional relationships along the distal nephron.” Because of the disappointing quality of the electromicrographs, this article is reprinted here.
Effect of amino acid intake on brush-border membrane uptake of sulfur amino acids
Authors: Chesney R. W. , Gusowski N. , Padilla M. , Lippincott S.
Published: December 2017

Alterations in the intake of sulfur amino acids (SAA) changes the rat renal brush-border membrane uptake of the beta-amino acid, taurine. A low-SAA diet enhances and a high-taurine diet reduces uptake (Chesney et al., Kidney Int. 24: 588-594, 1983). Neither the low-SAA diet nor the high-taurine diet alters the time course or concentration-dependent accumulation of the sulfur amino acids methionine and cystine or of inorganic sulfate. By contrast the uptake of beta-alanine, another beta-amino acid that competes with taurine, is greater in animals on the low-SAA diet. The high-taurine diet does not change beta-alanine uptake. The plasma levels of taurine are altered by dietary change, but not the values for methionine and cystine. This study indicates that renal adaptation is expressed for beta-alanine, a nonsulfur-containing beta-amino acid. By contrast, methionine, cystine, and sulfate, which participate in a variety of synthetic and conjugative processes, are not conserved by the renal brush-border surface following ingestion of either a low-methionine and -cystine diet or high-taurine diet.
Mechanism of chronic hypercalciuria with furosemide: increased calcium absorption
Authors: Bushinsky D. A. , Favus M. J. , Langman C. B. , Coe F. L.
Published: December 2017

Furosemide produces chronic hypercalciuria. The source of the additional urinary calcium is not known but must be either bone mineral or calcium absorbed by the intestine. Without bone calcium dissolution or increased absorption the filtered load of calcium would fall and urinary calcium excretion would return to pretreatment levels. To determine whether furosemide alters intestinal calcium absorption, we fed furosemide (75 mg . kg body-1 wt . day-1) to 11 rats eating 15 g/day of a 0.60% calcium diet. Compared with 11 control rats, furosemide increased urine calcium (15.6 +/- 0.8 mg/5 days vs. 4.1 +/- 0.3, P less than 0.001). Fecal calcium excretion fell (194 +/- 7 mg/5 days vs. 223 +/- 12, P less than 0.05), indicating an increase in intestinal calcium absorption sufficient to sustain the hypercalciuria. The increase in absorption occurred without an increase in the level of serum 1,25-dihydroxycholecalciferol (180 +/- 20 pg/ml vs. 220 +/- 16, furosemide vs. control, respectively, P = NS). To determine whether the intestinal effect of furosemide persists after the initial sodium diuresis abates, we analyzed only the last 3 days of balance. Again, rats fed furosemide had increased urine excretion and intestinal absorption of calcium, so that net calcium balance was not different from that of controls. Twelve additional rats were fed a 0.02% calcium diet to which 35 mg . kg body wt-1 . day-1 of furosemide was added. Compared with eleven controls, urine calcium increased and fecal calcium excretion again fell, but balance was not different. Chronic administration of furosemide increases intestinal calcium absorption enough to permit urine calcium excretion to remain elevated without the necessity for bone dissolution.
Amiloride reduces potassium conductance in frog kidney via inhibition of Na+-H+ exchange
Authors: Oberleithner H. , Munich G. , Schwab A. , Dietl P.
Published: December 2017

The existence of a carrier-mediated Na+-H+ exchange has been described recently in many epithelial and nonepithelial tissues including the diluting segment of the amphibian kidney. In this preparation the Na+-H+ exchanger is dramatically stimulated by so-called K+ adaptation (chronic exposure of animals to high potassium) and completely inhibited by the diuretic drug amiloride. We performed electrophysiological experiments in diluting segments of the isolated perfused frog kidney to investigate whether amiloride affects the conductance properties of this epithelium. Amiloride dramatically increased the transepithelial resistance and the ratio of lumen over peritubular cell membrane resistance. Cell membrane potential changes, induced by luminal K+ concentration steps, were blunted by luminal application of amiloride, by luminal Na+-free perfusates, or by acidification of the kidney perfusion solution. K+ secretory net flux, measured by K+-sensitive microelectrodes, decreased by half in presence of the diuretic. The experiments reveal that amiloride reduces the K+ conductance of the luminal cell membrane of frog diluting segment via inhibition of the luminal Na+-H+ exchanger. This decreases transepithelial K+ net secretion in this nephron segment.
Vasopressin increases cytosolic free calcium concentration in glomerular mesangial cells
Authors: Bonventre J. V. , Skorecki K. L. , Kreisberg J. I. , Cheung J. Y.
Published: December 2017

Cytosolic free calcium concentration ([Ca2+]f) was determined in cultured rat glomerular mesangial cells under basal conditions and after exposure to arginine vasopressin (AVP) or angiotensin II (ANG II). [Ca2+]f was determined using quin 2 or fura-2, two intracellular fluorescent probes. [Ca2+]f was measured to be 102 +/- 3 nM (n = 154) using quin 2 and 82 +/- 4 (n = 34) using fura-2. AVP and ANG II increased [Ca2+]f. Maximal levels of [Ca2+]f were achieved in less than 10 s after addition of the hormone. This peak value was followed by a rapid fall toward the base line. With fura-2 as the intracellular Ca2+ indicator, [Ca2+]f increased from 74 +/- 7 to a peak of 578 +/- 39 nM (n = 17) with 100 nM AVP. At 115 s after addition of AVP, [Ca2+]f was 125 +/- 9 nM. Similar peak levels of [Ca2+]f were observed using quin 2. The increase in [Ca2+]f was due in large part to release of Ca2+ from intracellular stores, since reduction in extracellular free [Ca2+] with EGTA did not prevent the hormone-induced increase in [Ca2+]f, although it did result in a decreased peak level and a more rapid return to base line. The AVP-induced increase in [Ca2+]f was blocked by the V1 receptor antagonist (CH2)5Tyr(Me)VDAVP. Neither isoproterenol, which increased adenylate cyclase activity, nor dibutyryl cAMP had any affect on [Ca2+]f directly or on the AVP-induced increase in [Ca2+]f. In this report we present the first direct measurements of [Ca2+]f and hormone-induced changes in [Ca2+]f in glomerular mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of synthetic ANP on renal and loop of Henle functions in the young rat
Authors: Roy D. R.
Published: December 2017

The present studies were undertaken to determine, by recollection micropuncture, the effect of a synthetic atrial natriuretic peptide (ANP) on the absolute and fractional deliveries of water and sodium to the juxtamedullary end-descending limb. Two groups of young female Munich-Wistar rats were studied: control (n = 8) received the vehicle only; and ANP (n = 12) received a prime followed by the constant infusion of a synthetic rat atrial peptide (28 amino acids). With the infusion of ANP, clearance of p-[14C]aminohippurate [( 14C]PAH) and glomerular filtration rate (GFR) fell significantly. Despite this fall in GFR and renal plasma flow, ANP produced a 2-fold increase in urine volume and a 10-fold increase in sodium excretion. Absolute and fractional sodium deliveries to the end-descending limb increased by approximately 30% in the ANP group, whereas mean juxtamedullary single-nephron glomerular filtration rate (SNGFR) remained stable. In three additional rats prepared for micropuncture of the superficial end-accessible proximal tubule, ANP reduced cortical SNGFR by approximately 15%. By contrast, GFR did not decline in response to ANP in larger rats, when treated identically. We conclude that in young rats ANP can produce a natriuresis in the absence of a rise in GFR; the fall in GFR observed following ANP is due presumably to the immaturity of the animals used in these studies; and ANP produces a rise in absolute and fractional water and sodium deliveries to the end-descending limb that cannot be attributed to a change in SNGFR.(ABSTRACT TRUNCATED AT 250 WORDS)
Amiloride-inhibited Na+-H+ exchange in human kidney medulla microsomes
Authors: LaBelle E. F.
Published: December 2017

Membrane vesicles from the medulla of the human kidney are capable of amiloride-inhibited sodium-proton exchange. Sodium uptake into the vesicles is stimulated by low intravesicular pH (6.0) and inhibited by both low extravesicular pH (6.0) and amiloride (2 mM). Sodium uptake is a linear function of the vesicular protein concentration and can be reversed by raising the osmotic strength of the solution to shrink the vesicles or by adding the ionophore nigericin. Acridine orange was accumulated by the vesicles in response to a pH gradient (pH 6.0, inside, 8.0 outside), and the accumulation of acridine orange could be reduced by increased extravesicular sodium. Thus sodium could stimulate proton movement just as protons could stimulate sodium movement across the vesicular membrane.
Renal reabsorption of phosphate during development: whole-kidney events
Authors: Johnson V. , Spitzer A.
Published: December 2017

The isolated perfused kidney of the guinea pig has been used to assess the mechanism that accounts for the maintenance of the positive phosphate (Pi) balance during development. The kidneys obtained from mature guinea pigs (n = 25) had a glomerular filtration rate (GFR) of 0.48 +/- 0.04 ml/min (mean +/- SE), whereas those of the newborn (n = 20) had a GFR of 0.15 +/- 0.02 ml/min. These values compare favorably with those observed in intact animals. The fractional excretion of Na+ (FENa) was 3.8 +/- 0.7% in the mature kidneys and 4.7 +/- 0.7% in the newborn kidneys. The maximal tubular reabsorption of Pi (TmPi) by the newborn kidney was 24.3 +/- 2.8 micrograms/min. The filtered load at which the TmPi of the newborn was reached exceeds by 2.5-fold the filtered load of Pi encountered under physiological conditions. In the adult the TmPi was 53.9 +/- 2.6 micrograms/min. The filtered load at which the TmPi of the adult was reached is only slightly higher than the average normal filtered load of Pi. The TmPi/GFR was significantly higher (P less than 0.02) in the newborn (117.4 +/- 10.8 micrograms X min-1 X ml-1 GFR) compared with the adult (82.6 +/- 3.6 micrograms X min-1 X ml-1 GFR). Moreover, at any filtered load of Pi below Tm the newborn animals reabsorbed twofold more Pi per gram kidney weight than the adult (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Role of proximal convoluted tubule in pressure diuresis in the rat
Authors: Chou C. L. , Marsh D. J.
Published: December 2017

The role of different nephron segments in the diuretic response to acute arterial hypertension was studied with tubular microperfusion. Early proximal convolutes were perfused with synthetic glomerular ultrafiltrate; fluid was collected from the last visible loop of the same proximal or from the first loop of the distal tubule. In late proximal collections, an increase of arterial pressure of 24 +/- 2 mmHg reduced reabsorption of tubular fluid 44 +/- 4%. Perfusate chloride concentration fell, but only 2 meq/liter, so that chloride reabsorption was inhibited in proportion to the inhibition of fluid reabsorptions, with a corresponding increase in chloride delivery to the loop of Henle. In early distal collections, there was no significant difference of the early distal flow rate with hypertension, but early distal chloride concentration increased 31 +/- 8% and chloride load increased 45 +/- 12%. Qualitatively similar increases were obtained from paired collections made from free-flowing early distal tubules. Inhibition of proximal fluid reabsorption is a primary response to acute hypertension and may contribute to pressure diuresis. In addition, this inhibition increases the strength of the luminal signal to the macula densa, enhancing the autoregulatory response to hypertension.
Mechanisms controlling renal hemodynamics and electrolyte excretion during amino acids
Authors: Woods L. L. , Mizelle H. L. , Montani J. P. , Hall J. E.
Published: December 2017

Our purpose was to investigate the mechanisms by which increased plasma amino acids elevate renal blood flow (RBF) and glomerular filtration rate (GFR). Since transport of amino acids and Na+ is linked in the proximal tubule, we hypothesized that increased amino acids might stimulate proximal tubular Na+ reabsorption (PRNa) and thus increase RBF and GFR by a macula densa feedback mechanism. A solution of four amino acids (Ala, Ser, Gly, Pro) was infused intravenously (0.075 mmol X kg-1 X min-1 total) into anesthetized dogs with normal kidneys (NK) and with kidneys in which the tubuloglomerular feedback mechanism was blunted by lowering renal artery pressure (LPK) or blocked by making the kidneys nonfiltering (NFK). In NK, RBF and GFR increased by 35 +/- 4% and 30 +/- 7% after 90 min of amino acid infusion, while PRNa (estimated from lithium clearance) and O2 consumption increased by 31 +/- 5% and 29 +/- 5% and distal Na+ delivery remained relatively constant. Autoregulation of RBF and GFR in response to step decreases in renal artery pressure was impaired during amino acids in NK. The hemodynamic responses to amino acids were abolished in LPK and NFK. Infusion of the nonmetabolized alpha-aminoisobutyric acid (0.075 mmol X kg-1 X min-1) into NK produced changes in renal hemodynamics that were similar to the responses observed with the four metabolizable amino acids. These data are consistent with the hypothesis that elevation of plasma amino acids increases RBF and GFR by a mechanism that requires an intact macula densa feedback. Metabolism of the amino acids does not appear to be necessary for these changes to occur.