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1.
Administration of atrial natriuretic factor inhibits sodium-coupled transport in proximal tubules. 总被引:3,自引:1,他引:2
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T G Hammond A N Yusufi F G Knox T P Dousa 《The Journal of clinical investigation》1985,75(6):1983-1989
The newly discovered peptides extracted from cardiac atria, atrial natriuretic factors (ANFs), when administered parenterally cause renal hemodynamic changes and natriuresis. The nephron sites and cellular mechanism accounting for profound increase in Na+ excretion in response to ANFs are not yet clarified. In the present study we investigated whether synthetic ANF peptide alters the reabsorption of Na+ and reabsorption of solutes cotransported with Na+ in the proximal tubules of rats. Synthetic ANF peptide consisting of 26 amino acids, 4 micrograms/kg body wt/h, or vehicle in controls, was infused to surgically thyroparathyroidectomized anesthetized rats. After determination of the fractional excretion (FE) of electrolytes (Na+, K+, Pi, Ca2+, Mg2+, HCO3), the kidneys were removed and luminal brush border membrane vesicles (BBMVs) were prepared from renal cortex. Solute transport was measured in BBMVs by rapid filtration techniques. Infusion of ANF peptide increased FENa, FEPi, and FEHCO3; but FECa, FEK, and FEMg were not changed. The increase in FENa was significantly correlated, on the one hand, with increase of FEPi (r = 0.9, n = 7; P less than 0.01) and with increase of FEHCO3 (r = 0.89, n = 7; P less than 0.01). On the other hand, FENa did not correlate with FEK, FECa, or with FEMg. The Na+ gradient-dependent uptake of Pi by BBMVs prepared from renal cortex of rats receiving ANF infusion was significantly (P less than 0.05) decreased (-25%), whereas the Na+ gradient-dependent uptake of L-[3H]proline and of D-[3H]glucose or the diffusional uptake of 22Na+ were not changed. ANF-elicited change in FEPi showed a close inverse correlation with decrease of Na+-dependent Pi uptake by BBMVs isolated from infused rats (r = 0.99, n = 7; P less than 0.001). Direct addition of ANF to BBMVs in vitro did not change the Na+ gradient-dependent Pi uptake. In rats infused with ANF, the rate of amiloride-sensitive Na+-H+ exchange across the brush border membrane (BBM) was significantly (P less than 0.05) decreased (-40%), whereas the diffusional 22Na+ uptake (0.5 min) and the equilibrium (120 min) uptake of 22Na+ were not changed. The inhibition of Na+-H+ exchange after ANF was likely due to alteration of the BBM antiporter itself, in that the H+ conductance of BBMVs was not increased. We conclude that synthetic ANF (a) decreases tubular Na+ reabsorption linked to reabsorption of HCO3 in proximal tubules, and (b) inhibits proximal tubular reabsorption of Pi coupled to Na+ reabsorption, independent of secretion and/or action of parathyroid hormone or calcitonin. These ANF effects are associated with inhibition of Na+-Pi synport and of Na+-H+ antiport in luminal BBMs. Our findings document that inhibition of Na+-coupled transport processes in proximal tubules is an integral part of the renal response to ANF. 相似文献
2.
Calcium transport in canine renal basolateral membrane vesicles. Effects of parathyroid hormone. 总被引:1,自引:5,他引:1
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The effects of parathyroid hormone were studied on Ca2+ fluxes in canine renal proximal tubular basolateral membrane vesicles (BLMV). Efflux of Ca2+ from preloaded BLMV was found to be stimulated by an external Na+ gradient, and this was inhibited by the Na+ ionophore, monensin, and enhanced by intravesicular negative electrical potentials, which indicated electrogenic Na+/Ca2+ exchange activity. There was a Na+ gradient independent Ca2+ flux, but membrane binding of Ca2+ was excluded from contributing to the Na+ gradient-dependent efflux. The Na+ gradient-dependent flux of Ca2+ was very rapid, and even 2- and 5-s points may not fully represent absolute initial rates. It was saturable with respect to the interaction of Ca2+ and Na+ with an apparent (5 s) Km for Na+-dependent Ca2+ uptake of 10 microM, and an apparent (5 s) Vmax of 0.33 nmol/mg protein per 5 s. The Na+ concentration that yielded half maximal Ca2+ efflux (2 s) was 11 mM, and the Hill coefficient was two or greater. Both Na+ gradient dependent and independent Ca2+ efflux were decreased in BLMV prepared from kidneys of thyroparathyroidectomized (TPTX) dogs, and both were stimulated by parathyroid hormone (PTH) infusion to TPTX dogs. BLMV from TPTX dogs exhibited significantly reduced maximal stimulation of Na+ gradient-dependent Ca2+ uptake with an apparent (5 s) Vmax of 0.23 nmol/mg protein per 5 s, but the apparent Km was 8 microM, which was unchanged from normal. The Na+ gradient independent Ca2+ uptake was also reduced in BLMV from TPTX dogs compared with normal. Thus, PTH stimulated both Na+/Ca2+ exchange activity and Na+ independent Ca2+ flux. In vivo, the latter could result in an elevation of cytosolic Ca2+ by PTH, and this might contribute to the observed decrease in solute transport in the proximal tubule. 相似文献
3.
Effect of acute changes in glomerular filtration rate on Na+/H+ exchange in rat renal cortex.
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D A Maddox S M Fortin A Tartini W D Barnes F J Gennari 《The Journal of clinical investigation》1992,89(4):1296-1303
Studies were undertaken in Munich-Wistar rats to assess the influence of changes in filtered bicarbonate (FLHCO3), induced by changes in GFR, on Na+/H+ exchange activity in renal brush border membrane vesicles (BBMV). Whole-kidney and micropuncture measurements of GFR, FLHCO3, and whole-kidney and proximal tubule HCO3 reabsorption (APRHCO3) were coupled with BBMV measurements of H+ gradient-driven 22Na+ uptake in each animal studied. 22Na+ uptake was measured at three Na+ concentration gradients to allow calculation of Vmax and Km for Na+/H+ exchange. GFR was varied by studying animals under conditions of hydropenia, plasma repletion, and acute plasma expansion. The increase in GFR, FLHCO3, and APRHCO3 induced by plasma administration correlated directly with an increase in the Vmax for Na+/H+ exchange in BBMV. The Km for sodium was unaffected. In the plasma-expanded rats, the Vmax for Na+/H+ exchange was 22% greater than in the hydropenic rats (P less than 0.025) whereas APRHCO3 was 86% greater (P less than 0.001). These results indicate that increases in FLHCO3, induced by acute increases in GFR, stimulate Na+/H+ exchange activity in proximal tubular epithelium. This stimulation is a mechanism which can, in part, account for the delivery dependence of proximal bicarbonate reabsorption. 相似文献
4.
Increased renal catabolism of 1,25-dihydroxyvitamin D3 in murine X-linked hypophosphatemic rickets. 总被引:1,自引:2,他引:1
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The hypophosphatemic (Hyp) mouse, a murine homologue of human X-linked hypophosphatemic rickets, is characterized by renal defects in brush border membrane phosphate transport and vitamin D3 metabolism. The present study was undertaken to examine whether elevated renal 25-hydroxyvitamin D3-24-hydroxylase activity in Hyp mice is associated with increased degradation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] by side chain oxidation. Metabolites of 1,25(OH)2D3 were separated by HPLC on Zorbax SIL and identified by comparison with standards authenticated by mass spectrometry. Production of 1,24,25-trihydroxyvitamin D3, 24-oxo-1,25-dihydroxyvitamin D3, and 24-oxo-1,23,25-trihydroxyvitamin D3 was twofold greater in mitochondria from mutant Hyp/Y mice than from normal +/Y littermates. Enzyme activities, estimated by the sum of the three products synthesized per milligram mitochondrial protein under initial rate conditions, were used to estimate kinetic parameters. The apparent Vmax was significantly greater for mitochondria from Hyp/Y mice than from +/Y mice (0.607 +/- 0.064 vs. 0.290 +/- 0.011 pmol/mg per protein per min, mean +/- SEM, P less than 0.001), whereas the apparent Michaelis-Menten constant (Km) was similar in both genotypes (23 +/- 2 vs. 17 +/- 5 nM). The Km for 1,25(OH)2D3 was approximately 10-fold lower than that for 25-hydroxyvitamin D3 [25(OH)D3], indicating that 1,25(OH)2D3 is perhaps the preferred substrate under physiological conditions. In both genotypes, apparent Vmax for 25(OH)D3 was fourfold greater than that for 1,25(OH)2D3, suggesting that side chain oxidation of 25(OH)D3 may operate at pharmacological concentrations of substrate. The present results demonstrate that Hyp mice exhibit increased renal catabolism of 1,25(OH)2D3 and suggest that elevated degradation of vitamin D3 hormone may contribute significantly to the clinical phenotype in this disorder. 相似文献
5.
1,25-(OH)_2D_3减轻糖尿病大鼠炎症因子的排泄及podocin表达缺失 总被引:3,自引:1,他引:2
目的:观察1,25-(OH)2D3对糖尿病大鼠尿液炎症因子单核细胞趋化蛋白- 1(MCP-1)、肿瘤坏死因子-α(TNF-α)、干扰素-λ(IFN-λ)及podocin表达水平的影响。方法:雄性Wistar大鼠随机分为对照组和糖尿病模型组;后者经链脲菌素诱导糖尿病模型成功后再随机分为糖尿病组和1,25-(OH)2D3组。给予1,25-(OH)2D3第6周测定大鼠尿红细胞、24小时尿蛋白、MCP-1、TNF-α、IFN-λ排泄及血糖水平。肾组织光镜电镜、肾小球podocin免疫组化及荧光染色定量分析检测podocin的表达。结果:与对照组相比,1,25-(OH)2D3组及糖尿病组尿红细胞、尿蛋白、MCP-1、TNF-α、IFN-λ、血糖明显升高(P<0.01),podocin蛋白表达明显下降(P<0.01)。与糖尿病组相比,1,25-(OH)2D3组尿红细胞、尿蛋白、MCP-1、TNF-α、IFN-λ、血糖明显降低(P<0.05或P<0.01),podocin蛋白表达明显增加(P<0.01)。结论:1,25-(OH)2D3可减轻糖尿病大鼠血尿、蛋白尿,减轻尿液炎症因子的排泄,恢复podocin的表达而有肾保护作... 相似文献
6.
Adaptation of Na+-H+ exchange in renal microvillus membrane vesicles. Role of dietary protein and uninephrectomy. 总被引:3,自引:13,他引:3
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The ablation of renal mass and institution of a high protein diet both lead to renal cortical hypertrophy and increased glomerular filtration rate (GFR). We studied Na+ transport in rat microvillus membrane vesicles isolated from uninephrectomized or sham operated rats fed 6% (low), 24% (standard), or 40% (high) protein diets. The feeding of high protein, as compared with low protein, was associated with a 50% increase in rates of pH-stimulated 22Na+ transport in isolated vesicles from sham and uninephrectomized animals. Values for the standard protein diet were intermediate to values for high and low protein. At each level of dietary protein intake, vesicular Na+ transport was greater in the uninephrectomized than in sham rats. The high protein diet was also associated with increased vesicular 22Na+ flux inhibitable by 1 mM amiloride. Increases in total and amiloride sensitive flux were also noted in the absence of a pH gradient. Conductive Na+ and H+ transport were not altered, nor were sodium-glucose and sodium-alanine cotransport. Kinetic studies revealed evidence for an increased Vmax of Na+-H+ exchange in uninephrectomized animals fed a 40 vs. a 6% protein diet whereas Km was unchanged. Supplements of NaHCO3 in the 40% protein diet, to adjust for an increased rate of net acid excretion, did not prevent the increased rates of Na+-H+ exchange. However, treatment with actinomycin D (0.12 mg/kg) prevented the increased Na+-H+ activity as well as the increased renal mass and GFR noted 24 h after unilateral nephrectomy. Na+-H+ exchange rate was closely correlated with GFR (r = 0.961; P less than 0.005) and renal mass (r = .986; P less than 0.001). These observations provide evidence for modification of the luminal membrane Na+-H+ exchanger in response to changes in dietary protein content and nephron number. 相似文献
7.
Sodium influx in human leucocytes: a novel technique for assessment of sodium-proton antiport activity 总被引:1,自引:0,他引:1
1. A triple-isotope method for measuring initial 22Na uptake rates in unactivated human leucocytes in the presence of serum, using 3H2O, [14C]sucrose and 22Na, is described. 2. This 22Na influx is inhibited by amiloride, with half-maximal inhibition at a concentration of 10(-5) mol/l. 3. About 70% of the 22Na influx in normal human leucocytes is inhibited by 1 mmol/l amiloride, with an external Na+ concentration of 10 mmol/l. 4. External Na+ antagonizes this inhibition by amiloride. The Km for external Na+ is 9 mmol/l. 5. Intracellular acidification from either external Na+ depletion or ammonium chloride incubation leads to an activation of amiloride-sensitive Na+ influx. 6. The amiloride-sensitive Na+-H+ antiport provides the major influx pathway for Na+ in unactivated human leucocytes in the presence of serum. 相似文献
8.
Huang Chang-Quan Dong Bi-Rong Xiao Qian He Ping Ding Qun-Fang Lu Zhen-Chan Peng Xiao-Dong 《Journal of investigative medicine》2008,56(6):872-877
OBJECTIVE: The study aimed to explore the relationship among renal injury, abnormal vitamin D metabolism, and bone homeostasis in insulin resistance (IR) or type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: The animal models of IR, T2DM, and T2DM treated with 1-alpha hydroxyvitamin D (1-alphaOHD) were established on 18-month-old male Wistar rats. Glucose infusion rates (GIR) and levels of urinary albumin (UA), serum 25-hydroxyvitamin D (25-(OH)D), serum 1,25-dihydroxyvitamin D (1,25-OH2D), and bone mineral density (BMD) in lumbar vertebrae and femoral bone were measured. RESULTS: Urinary albumin level in the rats with T2DM significantly increased, and there existed a significant and negative correlation between GIR and UA level in the rats with T2DM or IR. The levels of serum 25-OHD in all models were similar. The levels of serum 1,25-OH2D and BMD in the rats with IR were significantly higher than those in the rats with T2DM and were lower than those in normal control rats. In the aged rats with T2DM, administration of 1-alphaOHD had no effect on serum 25-OHD level although significantly increased the levels of serum 1,25-O2D and BMD. There existed a negative correlation between the levels of serum 1,25-(OH)2D and UA in the rats with T2DM or IR. CONCLUSIONS: In IR or T2DM, abnormal vitamin D metabolism is characterized by 1,25-OH2D deficiency and is related to renal injury, and there also existed bone loss. In T2DM, both 1,25-(OH)2D deficiency and bone loss can be reversed by 1-alphaOHD. 相似文献
9.
OBJECTIVES: To investigate whether there is a relationship between serum 1,25 dihydroxy vitamin D3 [1,25(OH)2D3], which is an inhibitor of angiogenesis, concentrations and severity of diabetic retinopathy (DR). DESIGN AND METHODS: Serum 1,25(OH)2D3, 25 hydroxy vitamin D [25(OH)D] and parathormone (PTH) concentrations were measured in diabetic patients (n = 66) and nondiabetic healthy subjects (n = 20). RESULTS: The mean serum 1,25(OH)2D3 concentration in diabetic patients was lower than that in nondiabetics (57.3+/-21.44 vs. 89.4+/-18.01 pmol/L, p<0.001); mean 1,25(OH)2D3 concentrations fell with increasing severity of DR [being 63.4+/-17.26 pmol/L for background DR (BDR), 47.7+/-13.27 pmol/L for preproliferative DR (pre-PDR), and 43.1+/-19.45 pmol/L for proliferative DR (PDR)]. Compared with the control group, serum 25(OH)D concentrations were found to be decreased in diabetic patients (p<0.001).There were negative correlations between 1,25(OH)2D3 and age (r = -0.331, p<0.01) and duration of diabetes (r = -0.255, p<0.05). CONCLUSION: From these findings, it was found that there was an inverse relationship between the severity of the retinopathy, i.e., neovascularization, and serum 1,25(OH)2D3 concentrations, being the lowest in PDR and the highest in diabetic patients without retinopathy (NDR) patients. The measurement of serum 1,25(OH)2D3 concentrations might be helpful to predict severity of DR in patients with diabetes mellitus. 相似文献
10.
Nachman Brautbar Marlin W. Walling Jack W. Coburn John O. Steppe 《The Journal of clinical investigation》1979,63(2):335-341
To evaluate the role of vitamin D in the physiologic response to phosphorus depletion (P depleton) and the response to vitamin D administration in P depletion, we studied vitamin D-deficient (-D) rats, fed either a normal or low phosphorus diet and then injected intraperitoneally on alternate days with replacement vitamin D(3), 1.25 mug qod (D(3)); 1.25-dihydroxy-vitamin D(3)[1,25(OH)(2)D(3)] in physiologic, 54 ng qod (LD), and pharmacologic doses, 400 ng qod (HD); or vehicle alone (-D). The following results were obtained: (a) With P depletion, urinary excretion of inorganic phosphorus (Pi) fell to almost undetectable levels in -D rats, and two physiologic features of P depletion a calcemic effect and hypercalciuria, ensued. (b) With administration of vitamin D(3) or 1,25(OH)(2)D(3) in either doses to P-depleted rats, the renal retention of Pi was unaltered despite a significant elevation of serum Pi. (c) The calcemic response to P depletion was accentuated by vitamin D sterols, and the hypercalciuria of P depletion was reduced by 1,25(OH)(2)D(3), HD > LD > D(3). (d) In -D animals receiving normal Pi (+P), D(3), and 1,25(OH)(2)D(3), both LD and HD produced a significant calcemic and phosphatemic effect. (e) Urinary Pi excretion in +P animals was reduced slightly by vitamin D(3) whereas 1,25(OH)(2)D(3), both LD and HD, lowered urinary Pi markedly despite an increased serum Pi. (f) The serial values of serum Ca and Pi and urinary Ca in PD rats and the sequential values for urinary and serum Pi in +P rats indicated more rapid effects of 1,25(OH)(2)D(3), both HD and LD, compared with D(3). We conclude that: (a) The renal adaptation and physiologic response to PD does not require the presence of vitamin D. (b) 1,25(OH)(2)D(3) may directly enhance the renal tubular reabsorption of Pi even as serum Pi rises. (c) A hypocalciuric action of 1,25(OH)(2)D(3) in rats on low phosphorus diet could be direct or occur as a consequence of an increase in serum Pi produced by 1,25(OH)(2)D(3). The different sequential renal response to D(3) compared with 1,25-(OH)(2)D(3) raises the possibility that other natural forms of vitamin D(3) [i.e., 25(OH)D(3), 24,25(OH)(2)D(3), etc.] which may be present in vitamin D-fed rats but not those given only 1,25(OH)(2)D(3), could modify the actions of 1,25(OH)(2)D(3). 相似文献
11.
Evidence that blood ionized calcium can regulate serum 1,25(OH)2D3 independently of parathyroid hormone and phosphorus in the rat.
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D A Bushinsky G S Riera M J Favus F L Coe 《The Journal of clinical investigation》1985,76(4):1599-1604
This study asks whether arterial blood ionized calcium concentration (Ca++) can regulate the serum level of 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] independently of serum phosphorus and parathyroid hormone (PTH). We infused either PTH (bovine 1-34, 10 U/kg body wt/h) or saline into awake and unrestrained rats for 24 h, through a chronic indwelling catheter. PTH raised total serum calcium and arterial blood ionized calcium, yet serum 1,25(OH)2D3 fell from 35 +/- 6 (mean +/- SEM, n = 10) with saline to 12 +/- 3 pg/ml (n = 11, P less than 0.005 vs. saline). To determine if the decrease in serum 1,25(OH)2D3 was due to the elevated Ca++, we infused PTH into other rats for 24 h, along with varying amounts of EGTA. Infusion of PTH + 0.67 micron/min EGTA reduced Ca++, and 1,25(OH)2D3 rose to 90 +/- 33 (P less than 0.02 vs. PTH alone). PTH + 1.00 micron/min EGTA lowered Ca++ more, and 1,25(OH)2D3 increased to 148 +/- 29 (P less than 0.01 vs. saline or PTH alone). PTH + 1.33 micron/min EGTA lowered Ca++ below values seen with saline or PTH alone, and 1,25(OH)2D3 rose to 267 +/- 46 (P less than 0.003 vs. all other groups). Thus, during PTH infusion lowering Ca++ with EGTA raised 1,25(OH)2D3 progressively. There were no differences in serum phosphorus concentration or in arterial blood pH in any group infused with PTH. The log of serum 1,25(OH)2D3 was correlated inversely with Ca++ in all four groups infused with PTH (r = -0.737, n = 31, P less than 0.001), and also when the saline group was included (r = -0.677, n = 41, P less than 0.001). The results of this study indicate that serum 1,25(OH)2D3 may be regulated by Ca++ independent of PTH and serum phosphorus levels in the rat. Since 1,25(OH)2D3 regulates gastrointestinal calcium absorption, there may be direct feedback control of 1,25(OH)2D3, by its regulated ion, Ca++. 相似文献
12.
Vitamin D metabolites in diabetic patients: decreased serum concentration of 24,25-dihydroxyvitamin D 总被引:1,自引:0,他引:1
C Christiansen M S Christensen P McNair B Nielsen S Madsbad 《Scandinavian journal of clinical and laboratory investigation》1982,42(6):487-491
In order to elucidate if changes in vitamin D metabolism play a role for diabetic bone loss, the serum concentrations of the major vitamin D metabolites were studied in 26 adult male ambulatory insulin-treated diabetics, selected to have normal renal function and a duration of diabetes below 11 years. The patients were studied during usual metabolic control and exhibited wide ranges of hyperglycaemia and glycosuria. The serum concentrations of the major metabolites of vitamin D, 25-hydroxyvitamin D(2 + 3) (25OHD), 24,25-dihydroxyvitamin D(2 + 3) (24,25(OH)2D), and 1,25-dihydroxyvitamin D(2 + 3) (1,25(OH)2D), were measured in diabetics, and in age and sex matched controls. The diabetics had slightly decreased serum levels of 25OHD (42.0 nmol/l versus 55.5 nmol/l in normals, P less than 0.05), markedly decreased serum levels of 24,25(OH)2D (2.98 nmol/l versus 5.91 nmol/l, P less than 0.01), but serum levels of 1,25(OH)2D were virtually normal (64.2 pmol/l versus 68.3 pmol/l, ns). The close correlation between serum concentrations of 25OHD and 24,25(OH)2D observed in the normal subjects, was absent in the diabetics. There were no correlations between the serum levels of any of the vitamin D metabolites and the measured indices of glucose and calcium metabolism. It is concluded that insulin-dependent diabetic patients demonstrate definite alterations in serum levels of vitamin D metabolites, the significance of which remains unknown at present. 相似文献
13.
目的探讨良性原发性甲状旁腺功能亢进症(primary hyperparathyproidism,PHPT)患者血清1,25-二羟基维生素D3[1,25-dihydroxyvitamin D3,1,25(OH)2D3]水平变化及与甲状旁腺激素(parathyroid hormone,PTH)、血钙、血磷的关系。方法良性PHPT患者56例为观察组,同期体检健康者1118例为对照组,采用电化学发光法检测2组血清1,25(OH)2D3、PTH水平,比色法测定血钙水平,磷钼酸盐法测定血磷水平。比较2组维生素D缺乏[1,25(OH)2D3<20μg/L]、严重缺乏[1,25(OH)2D3<10μg/L]的比率及不同年龄分层患者血清1,25(OH)2D3水平变化,Pearson法分析观察组维生素D缺乏、严重缺乏患者血清1,25(OH)2D3与PTH、血钙及血磷的相关性。结果观察组维生素D缺乏比率、严重缺乏比率(94.64%、46.43%)高于对照组(62.79%、14.13%)(P<0.05);Pearson相关分析显示,观察组血清1,25(OH)2D3与PTH、血钙及血磷均无线性相关性(r=-0.226,P=0.352;r=-0.274,P=0.256;r=0.073,P=0.593)。观察组年龄18~40岁、>40~60岁、>60岁患者血清1,25(OH)2D3[(10.76±3.17)、(10.61±5.01)、(10.72±4.85)μg/L]低于对照组[18~40岁:(18.19±9.86)μg/L,>40~60岁:(17.18±9.19)μg/L,>60岁:(17.91±10.52)μg/L](P<0.05);观察组维生素D缺乏患者血清PTH[(818.86±233.49)ng/L]、血钙[(2.98±0.59)mmol/L]、血磷[(0.78±0.17)mmol/L]与维生素D严重缺乏患者[(640.09±622.69)ng/L、(2.96±0.69)mmol/L、(0.75±0.20)mmol/L]比较差异无统计学意义(P>0.05);观察组维生素D缺乏、严重缺乏患者血清1,25(OH)2D3与PTH(r=-0.360,P=0.060;r=0.071,P=0.723)、血钙(r=-0.225,P=0.250;r=-0.228,P=0.252)、及血磷(r=0.239,P=0.221;r=-0.208,P=0.297)均无线性相关。结论良性PHPT患者血清1,25(OH)2D3低于正常人群,维生素D缺乏比率较高,且血清1,25(OH)2D3与PTH、血钙及.血磷无线性相关。 相似文献
14.
Pathophysiology of spontaneous hypercalciuria in laboratory rats. Role of deranged vitamin D metabolism.
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Recent data suggest a causal role of deranged 1,25(OH)2D metabolism in the syndrome of idiopathic hypercalciuria. To test this hypothesis, we evaluated if vitamin D availability and/or increased serum 1,25(OH)2D were critical for the expression of hypercalciuria in laboratory rats. Ca balance, serum 25OHD3, and 1,25(OH)2D3 were studied in D-deprived (-D) and D-repleted (+D) male progeny (p) born to normocalciuric (NC) and spontaneously hypercalciuric (SH) rats. 7 of the 14 pSH and 2 of 21 pNC had SH, which was defined as urinary Ca greater than two standard deviations above the mean of values for control animals on days 5 and 6 of a low Ca +D diet (1.19 vs. 0.58 mg/d, P less than 0.001). Fasting serum Ca and 25OHD3 were similar to control. Serum 1,25(OH)2D3 was elevated in these nine SH rats (232 vs. 145 pg/ml, P less than 0.005). However, during vitamin D deprivation, their Ca excretion was also increased (1.53 vs. 0.45 mg/d, P less than 0.001), despite comparably reduced serum 1,25(OH)2D3 (102 vs. 106 pg/ml) and undetectable serum 25OHD3. Net intestinal Ca absorption on a low Ca diet was comparable during D repletion (-0.75 vs. -0.82 mg/d) or D deprivation (-0.80 vs. -2.15 mg/d), excluding primary hyperabsorption as the mediator of the hypercalciuria. Mild hypophosphatemia was present in SH on +D (5.8 vs. 6.9 mg/dl, P less than 0.005) and -D diets (6.2 vs. 7.9 mg/dl, P less than 0.005), and was associated with higher rates of cyclic adenosine monophosphate excretion (32.8 vs. 26.9 and 48.5 vs. 41.0 nmol/mg of creatinine, respectively). Spontaneous hypercalciuria is therefore dissociable from increased Ca absorption, serum levels of 25OHD3, or 1,25(OH)2D3. The data are most compatible with the hypothesis of a renal Ca leak which stimulates parathyroid hormone activity and increases serum 1,25(OH)2D3, if provided adequate 25OHD3 as substrate. 相似文献
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Potassium depletion increases luminal Na+/H+ exchange and basolateral Na+:CO3=:HCO3- cotransport in rat renal cortex. 总被引:1,自引:7,他引:1
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M Soleimani J A Bergman M A Hosford T D McKinney 《The Journal of clinical investigation》1990,86(4):1076-1083
Most HCO3- reabsorption in proximal tubules occurs via electroneutral Na+/H+ exchange in brush border membranes (BBMS) and electrogenic Na+:CO3=:HCO3- cotransport in basolateral membranes (BLMS). Since potassium depletion (KD) increases HCO3- reabsorption in proximal tubules, we evaluated these transport systems using BBM and BLM vesicles, respectively, from control (C) and KD rats. Feeding rats a potassium deficient diet for 3-4 wk resulted in lower plasma [K+] (2.94 mEq/liter, KD vs. 4.47 C), and higher arterial pH (7.51 KD vs. 7.39 C). KD rats gained less weight than C but had higher renal cortical weight. Influx of 1 mM 22Na+ at 5 s (pHo 7.5, pHi 6.0, 10% CO2, 90% N2) into BLM vesicles was 44% higher in the KD group compared to C with no difference in equilibrium uptake. The increment in Na+ influx in the KD group was DIDS sensitive, suggesting that Na+:CO3=:HCO3- cotransport accounted for the observed differences. Kinetic analysis of Na+ influx showed a Km of 8.2 mM in KD vs. 7.6 mM in C and Vmax of 278 nmol/min/mg protein in KD vs. 177 nmol/min/mg protein in C. Influx of 1 mM 22Na+ at 5 s (pHo 7.5, pHi 6.0) into BBM vesicles was 34% higher in the KD group compared to C with no difference in equilibrium uptake. The increment in Na+ influx in the KD group was amiloride sensitive, suggesting that Na+/H+ exchange was responsible for the observed differences. Kinetic analysis of Na+ influx showed a Km of 6.2 mM in KD vs. 7.1 mM in C and Vmax of 209 nmol/min/mg protein in KD vs. 144 nmol/min/mg protein in C. Uptakes of Na(+)-dependent [3H]glucose into BBM and [14C]succinate into BLM vesicles were not different in KD and C groups, suggesting that the Na+/H+ exchanger and Na+:CO3=:HCO3- cotransporter activities were specifically altered in KD. We conclude that adaptive increases in basolateral Na+:CO3=:HCO3- cotransport and luminal Na+H+ exchange are likely responsible for increased HCO3- reabsorption in proximal tubules of KD animals. 相似文献
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The development of the Na/H antiporter was studied in renal brush border membrane vesicles (BBMV) from fetal and adult rabbits using isotopic and fluorescent techniques. The kinetics of the antiporter studied by 22Na+ uptake revealed that the Vmax was only 25% of that in the adult; however, the Km's for Na+ were not significantly different. These data were confirmed by a fluorescent assay using the pH-sensitive probe, acridine orange: the Vmax was significantly lower in the fetal BBMV. Conductive Na+ movement was estimated from amiloride-insensitive 22Na+ uptake and the rate of alkalinization induced by K+, an ion whose relative conductance was found to be similar to that of Na+. Although relative Na+ conductance was significantly greater in fetal BBMV, the lower Vmax in fetal vesicles could not be ascribed to this factor. Maternal administration of betamethasone (50 micrograms/kg intramuscularly) for 2 d before delivery significantly increased the Vmax of the antiporter to levels observed in the adult; Km was unaffected. Na/K ATPase activity increased fourfold after betamethasone, but the specific activities of four brush border marker enzymes and the kinetics of Na(+)-glucose cotransport were unchanged. These data indicate that there is a developmental increase in brush border Na/H exchange which is the result of an increase in the number and/or the turnover number of the carriers. Further, these data suggest that the postnatal increase in antiporter activity may be related to the surge in glucocorticoid concentration that occurs perinatally. 相似文献
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J Main N Velasco S D Heyes P Whiting R A Fraser G R Catto 《Clinical science (London, England : 1979)》1986,71(5):539-543
Uraemic rats maintained on either a high or a low phosphate diet for 12 weeks were allocated to one of the following oral vitamin D treatment groups and received: 1,25-dihydroxycholecalciferol [1, 25-(OH)2D3], 24,25-dihydroxycholecalciferol [24,25-(OH)2D3], both 1,25-(OH)2D3 and 24,25-(OH)2D3, or no vitamin D supplements. Mean serum creatinine concentrations were elevated to a similar extent in all groups. Mean serum concentrations of calcium, phosphate and alkaline phosphatase were not significantly different from normal in any of the groups. In the group receiving the high phosphate diet and no vitamin D supplements, calcified bone area measured by quantitative computerized histomorphometry was significantly lower than in the group receiving the low phosphate diet and no vitamin D supplements (0.01 greater than P greater than 0.001), and in the groups receiving high phosphate diet and either 1,25-(OH)2D3 (0.01 greater than P greater than 0.001) or 24,25-(OH)2D3 (0.01 greater than P greater than 0.001). We conclude that uraemic rats maintained on a high phosphate diet for 12 weeks develop skeletal demineralization, this process does not occur in rats on a low phosphate diet, and a decrease in calcified bone area may be prevented by treatment with either 1,25-(OH)2D3 or 24,25-(OH)2D3. 相似文献
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Huang CQ Ma GZ Tao MD Ma XL Feng J Liu QX 《The Journal of international medical research》2008,36(2):289-295
Insulin resistance (IR), IR treated with vitamin D, IR treated with 1alpha-hydroxyvitamin D (1alpha-(OH)D), type 2 diabetes mellitus (T2DM), T2DM treated with vitamin D and T2DM treated with 1alpha-(OH)D were studied in animal models using aged Wistar rats. Glucose infusion rates and levels of urinary albumin (UA), serum 25-hydroxyvitamin D (25-(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. T2DM rats had higher UA than IR or normal rats, and levels of 25-(OH)D in all models weresimilar. IR rats had higher 1,25-(OH)2D levels than T2DM rats, and had lower 1,25-(OH)2D levels than normal rats. Treating IR or T2DM rats with vitamin D had no effect on 25-(OH)D or 1,25-(OH)2D. Administration of 1alpha-(OH)D significantly increased 1,25-(OH)2D in IR rats to above-normal levels, and significantly increased 1,25-(OH)2D in T2DM rats to normal levels. In IR or T2DM, abnormal vitamin D metabolism is characterized by 1,25-(OH)2D deficiency and is related to renal injury. 相似文献
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Vervoort G Elving LD Wetzels JF Lutterman JA Smits P de Pont JJ Berden JH 《European journal of clinical investigation》2002,32(2):93-99
BACKGROUND: It has been reported that sodium-lithium countertransport (Na/Li CT) activity is increased in patients with diabetes mellitus and that this increased Na/Li CT activity is associated with the development of diabetic nephropathy. It is unclear however, whether Na/Li CT is related to other pathophysiological factors in diabetic patients. We studied kinetic parameters of Na/Li CT activity together with other putative risk factors for microangiopathy in normoalbuminuric type 1 diabetic patients and matched control subjects. SUBJECTS AND METHODS: We measured maximum velocity (Vmax) and sodium affinity (Km) of Na/Li CT in 53 diabetic patients and 45 healthy controls. Endothelial function was assessed by monitoring forearm vascular response to intrabrachial infusion of acetylcholine. Blood samples were collected for measurement of HbA1c, glucose, insulin and lipids. Blood pressure was measured intra-arterially. Renal haemodynamics were measured by inulin/p-aminohippurate clearance. Urinary albumin was measured by enzyme-linked immunosorbent assay. Transcapillary escape of albumin (TERalb) was calculated by the disappearance curve of 125I-labelled albumin. RESULTS: Vmax was increased in diabetic patients (779 +/- 36 micromol Li+ h-1 L-1 erythrocytes vs. 623 +/- 35 in controls, P < 0.01), whereas Km was decreased (64 +/- 16 mmol L-1 vs. 76 +/- 27 in controls, P = 0.03). The ratio of Vmax : Km was 12.4 +/- 0.6 in diabetic patients and 8.9 +/- 0.9 in controls (P < 0.001). When comparing diabetic patients in the lowest and highest quartile of Vmax or Km there were no differences in blood pressure, renal haemodynamics, urinary albumin excretion, TERalb, endothelial function, HbA1c, glucose, insulin, or lipid profile. CONCLUSION: Na/Li CT is increased in uncomplicated type 1 diabetes and characterized by an increase in Vmax and a decrease in Km. The increase in Na/Li CT is not associated with changes in endothelial function, degree of metabolic control, blood pressure or renal haemodynamics. 相似文献