Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were done in normal rats to assess kidney, single nephron, and tubuloglomerular feedback responses during renin-angiotensin blockade with the converting enzyme inhibitor (CEI) SQ 20881 (E. R. Squibb & Sons, Princeton, N. Y.) (3 mg/kg, per h). Converting enzyme inhibition was documented by complete blockade of vascular responses to infusions of angiotensin I (600 ng/kg). Control plasma renin activity was 12.5+/-2.7 ng angiotensin I/ml per h (mean+/-SEM) and increased sevenfold with CEI (n = 7). There were parallel increases in glomerular filtration rate from 1.08+/-0.05 to 1.26+/-0.05 ml/min and renal blood flow from 6.7+/-0.4 to 7.5+/-0.5 ml/min. During CEI infusion absolute and fractional sodium excretion were increased 10-fold. Proximal tubule and peritubular capillary pressures were unchanged. Single nephron glomerular filtration rate (SNGFR) was measured from both proximal and distal tubule collections; SNGFR based only on distal collections was significantly increased by CEI. A significant difference was observed between SNGFR values measured from proximal and distal tubule sites (6.0+/-1.6 nl/min) and this difference remained unchanged after CEI administration. Slight decreases in fractional absorption were suggested at micropuncture sites beyond the late proximal tubule, whereas early distal tubule flow rate was augmented by CEI. Tubuloglomerular feedback activity was assessed by measuring changes in proximal tubule stop-flow pressure (SFP) or SNGFR in response to alterations in orthograde microperfusion rate from late proximal tubule sites. During control periods, SFP was decreased 11.2+/-0.4 mm Hg when the perfusion rate was increased to 40 nl/min; during infusion of CEI, the same increase in perfusion rate resulted in a SFP decrement of 6.7+/-0.5 mm Hg (P<.001). When late proximal tubule perfusion rate was increased from 0 to 30 nl/min, SNGFR was decreased by 15.0+/-1.2 nl/min during control conditions, and by 11.3+/-1.3 nl/min during CEI infusion. Attenuation of feedback responsiveness during CEI was also observed at lower perfusion rates with both techniques. These results indicate that blockade of the renin-angiotensin system with CEI reduces the activity of the tubuloglomerular feedback mechanism which may mediate the observed renal vasodilation.
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PMID:Tubuloglomerular feedback and single nephron function after converting enzyme inhibition in the rat. 22 32

The response of the adenylate cyclase (AC) activity to PTH and calcitonin was measured along the nephron of normal (N) and mutant hypophosphatemic (Hyp) mice of the C 57 BL/6J strain, using in vitro single tubule AC microassay. In each experiment, a Hyp mouse was paired to a N mouse from the same litter. In the presence of PTH (10 U/ml), AC activities (femtomoles cAMP per millimeter of tubule per 30-min incubation) were reduced in the proximal convoluted tubule of Hyp mice as compared to N mice in all experiments (448 +/- (SEM) 46 vs. 831 +/- 79, N = 4, P less than 0.01). Some decrease in AC response to PTH also was noted in the cortical portion of the thick ascending limb of the loop of Henle (476 +/- 70 in Hyp mice vs. 719 +/- 83 in N mice, N = 4, P = NS). The Hyp and N AC responses to PTH were similar in the "bright" and "granular" portions of the distal convoluted tubule (1524 +/- 177 in Hyp mice and 1538 +/- 228 in N mice, N = 4). The other segments tested were not responsive to PTH (except the pars recta of the proximal tubule). In the presence of salmon calcitonin (10 ng/ml), a striking 5- to 12-fold increase in AC activity of the "bright" and "granular" portions of the distal convoluted tubule was observed in each Hyp mouse as compared to its paired N control (2434 +/- 618 vs. 399 +/- 56, N = 6, P less than 0.01). The AC response to calcitonin was also increased, though to a lesser extnet (Hyp/N = 1.8) in the "light" portion of the distal tubule (590 +/- 60 in Hyp and 352 +/- 36 in N mice, P less than 0.01). Other segments of the mouse nephron were also observed to contain calcitonin-sensitive AC, but the responses were of limited magnitude only and were not statistically different in Hyp and N mice. Dose-response curves showed that the decrease of the response to PTH in the proximal tubule as well as the increase of the response to calcitonin in the distal tubule were present in Hyp mice for the whole range of hormone concentrations tested. In both structures, the apparent Km for the cyclase activation by the hormone was similar in the Hyp and its paired N mouse.
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PMID:Hormone-sensitive adenylate cyclase along the nephron of genetically hypophosphatemic mice. 22 2

To determine if the glomerular filtration coefficient (Kf) of the dog is influenced by changes in plasma colloid osmotic pressure (COP), we conducted micropuncture experiments in dogs given concentrated albumin solutions. In one group (N = 9), filtration dynamics were evaluated following infusion of 450 to 600 ml of a 25% bovine albumin solution. To minimize the effects of acute volume expansion, we also achieved high COP levels in another group (N = 7) by albumin loading on the day prior to the experiment. In all experiments, renal arterial pressure was reduced to approximately 90 mm Hg to minimize potential errors that might lead to overestimation of single nephron filtration rate (SNGFR) and glomerular pressure (GP). In the acutely expanded dogs, COP increased to 23.0 +/- (SEM) 0.9 mm Hg, SNGFR was 59 +/- 6 nl/min, estimated GP was 61.0 +/- 2.0 mm Hg, proximal tubule pressure (PTP) was 23.0 +/- 1.6 mm Hg, and superficial filtration fraction (SFF) was 0.13 +/- 0.02. A similarly reduced whole kidney filtration fraction was also observed, due almost entirely to a marked increase in renal blood flow. When compared to noninfused control dogs (N = 13), Kf was significantly higher in the dogs with elevated COP, being 5.3 +/- 0.6 nl/min/mm Hg as compared to 3.4 +/- 0.3 nl/min/mm Hg. Average effective filtration pressure (EFP) was 12 +/- 1mm Hg, and EFP at the efferent end of the glomerular capillaries was 8.9 +/- 1.2 mm Hg. In the group infused on the prior day, COP was 20.0 +/- 0.8 mm Hg, SFF was 0.26 +/- 0.01, SNGFR was 70 +/-8 nl/min, GP was 59 +/- 2 mm Hg, and PTP was 19.0 +/- 1.5 mm Hg. Average EFP was 15 +/- 1 mm Hg, and EFP at the efferent end of the capillaries was 7.5 +/- 0.7 mm Hg. kf was 4.85 +/- 0.66 nl/min/mm Hg, a value significantly higher than that obtained in control dogs having a COP of 15.0 +/- 0.6 mm Hg. Furthermore, one group of control dogs (N = 4), expanded with an isooncotic albumin solution, did not exhibit significant changes in Kf even though the degree of plasma volume expansion was similar to the group expanded with concentrated albumin solution. These experiments are consistent with previous findings obtained in the rat that Kf is influenced by the COP, although the changes in Kf appear to be less than they are in the rat. The data indicate that even under these conditions of elevated COP, the filtration process in the dog is characterized by positive filtration pressures throughout the length of the glomerular capillaries.
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PMID:Glomerular filtration dynamics in the dog during elevated plasma colloid osmotic pressure. 48 Jul 83

Micropuncture studies demonstrate phosphate reabsorption in proximal tubules and between the late proximal and early distal convoluted tubule accessible to micropuncture. To further define the sites of phosphate reabsorption, the stationary microperfusion technique was applied to proximal and distal nephron segments. Phosphate reabsorption was evaluated in superficial loops of proximal tubules, descending segments beyound late proximal tubules accessible to micropuncture, ascending segments up to the point of micropuncture in the distal tubule, and superficial loops of distal tubules of thyroparathyroidectomized rats. Microperfusates of 1.3 or 2.6 nl (100 mmol/1 mannitol, 100 mmol/l NaCL, 32P-phosphate and 3H-inulin) were injected and then withdrawn after contact times of 2--108 s. Phosphate recovery relative to that of inulin was determined. A steep exponential decline of phosphate recovery (R) iwth increasing contact time (t) was observed in the superficial proximal tubule and descending segments. The slopes of the logarithmic regressions (10log R)/t, +/- SEM) were: -1.68 +/- 0.33 and -1.21 +/- 0.24min-1 in superficial proximal tubules and descending segments respectively. In contrast, no significant decline in phosphate recoveries (-0.02 +/- 0.04 and + 0.11 +/- 0.10 min-1) was apparent in the ascending segments and distal tubule. It is concluded that phosphate is reabsorbed in the proximal convoluted tubule and adjacent descending segments of the superficial nephron and that there is no significant phosphate reabsorption in distal convoluted tubules and adjacent ascending segments.
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PMID:Stationary microperfusion study of phosphate reabsorption in proximal and distal nephron segments. 55 98

Micropuncture studies were performed in rats infused with LiCl to induce stable plasma lithium concentrations of 2--3 mEq/l, or with an equivalent amount of NaCl. In free flow experiments LiCl reduced proximal tubule fractional reabsorption of sodium and potassium. Reduced reabsorption of bicarbonate, as reflected by a decrease in TF/PCl, was also observed. Proximal fractional reabsorption of chloride, however, was not affected. The TF/PIn at the end proximal tubule was 2.6 +/- 0.2 (mean +/- SEM) in controls and 2.1 +/- 0.1 in the experimental animals (P less than 0.025). In the distal portions of the nephron lithium treatment caused a fall in fractional reabsorption of water and sodium, while potassium secretion was stimulated in the distal tubule. Previous studies have indicated that lithium influences antidiuretic hormone stimulated water transport in the collecting duct. These experiments demonstrate that lithium also affects the transport of water and electrolytes in multiple nephron segments, including the proximal and distal convolution.
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PMID:Micropuncture study on the effects of lithium on proximal and distal tubule function in the rat kidney. 56 82

Scanning (SEM) and transmission (TEM) electron microscopy were used to elucidate morphological changes associated with acute tubular necrosis induced by high doses of mercuric chloride. Marked morphological changes were demonstrated in proximal tubules with TEM at one hour and with both SEM and TEM at six hours. These changes appeared earlier than reported in previous studies using any dose. The scanning microscopic provided a three-dimensional view of proximal cells showing changes in early injury with subsequent separation of the injured cells from the remaining cells. Certain of these residual cells change into low-lying cells with reline the proximal tubule. Variability was seen in the number of residual cells. However, once cell injury was initiated, necrosis proceeded in a reproducible manner.
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PMID:Scanning and transmission electron microscopy of mercuric chloride-induced acute tubular necrosis in rat kidney. 80 31

The stop-flow technique was used in dogs to determine the site of entry of urinary prostaglandins (PG) into tubular fluid. The proximal tubule was localized by the peak (U/PPAH)/(U/PIn) and the distal tubule and collecting duct by the peak U/PIn and the minimum (U/PNa)/(U/PIn). The peak of prostaglandin E (PGE) concentration was located 4.8+/-0.8 (SEM) ml distal to the proximal tubule and 4.6+/-0.8 (SEM) ml proximal to the distal nephron. At its peak, PGE was concentrated 6.3-fold over baseline, whereas inulin was concentrated 1.4-fold at its peak. The height of the PGE peak but not its location was increased by an i.v. infusion of angiotensin II at 20 ng/kg of body wt per min. Indomethacin abolished the PG peak. In a single experiment, prostaglandin F2alpha (PGF2alpha) exhibited an excretion pattern similar to PGE. These data indicate that the site of entry of PG into tubular fluid is most likely in the loop of Henle. This is consistent with the hypothesis that PG synthesized in the medulla can be transported to the cortex via tubular fluid. Whether PG in the tubular fluid can influence renal function remains to be determined.
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PMID:Urinary prostaglandins: site of entry into renal tubular fluid. 85 73

Simple dissection techniques of samples to be examined in the scanning electron microscope allow one to visualize easily the three-dimensional shape of epithelial cells in situ. Such preparations reveal a complex system of ridges and folds on the lateral surface of the cells whose intricacy can best be appreciated with SEM. In many epithelia there is a smooth apical band which corresponds to the region occupied by the junctional complex previously identified with conventional EM techniques. The secretion of chylomicra that result from a fatty meal can be observed. It is possible to study the distribution of concanavalin A binding sites on the lateral surfaces of the cells utilizing hemocyanin as a marker. In the case of the proximal tubule epithelium, the apical cell surface has many more binding sites than the lateral cell surface and there is a sharp demarcation at the level of the apical band. After blunt dissection the relationship of the basal surface of the cells with the basement lamina and the basement membrane can be appreciated as well. Possible physiological meaning of the morphological features observed is briefly discussed.
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PMID:Scanning electron microscopy of epithelia prepared by blunt dissection. 110 52

Reactive oxygen metabolites have been postulated to play an important role in both toxic and ischemic forms of acute renal tubular epithelial injury. In the present study, we examined the effect of enzymatically generated hydrogen peroxide on LLC-PK1 cells, a renal proximal tubule cell line. Exposure of LLC-PK1 cells to glucose and glucose oxidase (GO; which generates hydrogen peroxide) resulted in cytotoxicity (as measured by trypan blue exclusion) which was dose dependent and increased linearly over time to 81 +/- 5% at 180 minutes (8 +/- 1% at time 0; mean +/- SEM, N = 3 to 7). Catalase (which decomposes hydrogen peroxide) completely prevented the cytotoxicity, confirming that the toxicity was due to hydrogen peroxide production. To assess whether the hydrogen peroxide toxicity was a direct effect or mediated by other toxic oxygen metabolites, several scavengers of reactive oxygen metabolites and iron chelators were used. Superoxide dismutase (a scavenger of superoxide) had no effect. Deferoxamine (DFO), an iron chelator, provided marked protection (GO alone 45.9 +/- 4.4%; GO + DFO 13.0 +/- 2.0%; control 7.1 +/- 1.2%; N = 15 to 17, P less than 0.001). Pretreatment with DFO (1 hr, then 2 washes to remove DFO before GO addition) also markedly inhibited the cytotoxicity, suggesting that DFO's effect was due to iron chelation. Two other metal chelators (dihydroxybenzoic acid and 1,10-phenanthroline) also significantly decreased the GO-induced cytotoxicity. However, three of four hydroxyl radical scavengers used (mannitol, dimethyl sulfoxide, sodium benzoate) did not significantly decrease cell death. Only dimethylthiourea provided protection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydrogen peroxide cytotoxicity in LLC-PK1 cells: a role for iron. 166 14

The possible presence of lithium transport beyond the proximal tubule was examined by measuring lithium excretion after administration of triamterene, a potassium-sparing diuretic, exclusively acting in the cortical collecting tubule. Eight young and healthy volunteers were studied on two occasions during maximal water diuresis. After obtaining baseline values triamterene (100 mg orally) or placebo was administered, and measurements continued for 4 hours. Creatinine clearance was used as a marker of glomerular filtration rate, and phosphate excretion was used as an additional marker of proximal sodium transport. Compared to placebo (P), triamterene (T) caused a significant increase in fractional excretion of sodium (P, 0.74 +/- 0.08%; T, 1.73 +/- 0.24%, mean +/- SEM; P less than 0.01), and lithium (P, 21.2 +/- 1.3%; T, 27.5 +/- 1.5%; P less than 0.01), whereas fractional excretion of phosphate remained unchanged (P, 9.8 +/- 1.3%; T, 9.4 +/- 1.5%; P = NS). These results indicate that lithium is transported in the cortical collecting tubule, and provide further evidence that the use of lithium as a marker of purely proximal tubular sodium transport is of limited value.
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PMID:Triamterene increases lithium excretion in healthy subjects: evidence for lithium transport in the cortical collecting tubule. 251 83


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