Effect of prostaglandin E2 on adenylate cyclase activity in isolated glomeruli and tubules during postnatal maturation of rat renal cortex

To examine the effect of prostaglandins on adenylate cyclase during the postnatal maturation of kidney, the prostaglandin E2 (PGE2) responsiveness of adenylate cyclase in the absence and presence of exogenous GTP was investigated in glomeruli and tubules isolated from renal cortex of 14-, 21- and 30-day-old rats. In the absence of GTP, the adenylate cyclase response to PGE2 in glomeruli of 14-day-old rats was about fourfold higher than that in 21- and 30-day-old rats. In the tubules there was an about 30-35% decrease in the enzyme response to the prostaglandin between 14 and 21 days as well as between 21 and 30 days. When GTP was present, the PGE2 responsiveness of adenylate cyclase was of the same order of magnitude in glomeruli at 14 and 21 days and lower at 30 days. Under the same conditions, no significant changes were observed in the cortical tubules throughout the period studied. Thus association of PGE2 plus GTP suggests that during the postnatal maturation of rat kidney, the response of adenylate cyclase to PGE2 remains unchanged in cortical tubules and slightly decreases in glomeruli.     

Influence of Different Protein Intake on Renal Growth in Young Rats

ABSTRACT. We have examined the effect of high protein intake on kidney growth and function in growing rats. The rats were kept on an isocaloric diet containing 12%, 21% and 50% protein, from weaning (16 days) until the time of investigation (18, 20, 24,40 or 80 days). There was no significant difference between the 12% and 21% protein groups in any of the parameters studied. 50% protein increased body weight (BW) and kidney weight (KW). The increase in kidney weight was already evident after 2 days and exeeded the increase in body weight in all age groups. At 24 days renal cortical DNA and the protein/DNA ratio were significantly increased in the 50% protein group. At 40 days the cortical DNA content, but not the protein/DNA ratio, was significantly increased in the 50% group. The glomerular filtration rate (GFR) was studied at 40 days. Total GFR as well as GFR/BW was significantly higher in the 50% group than in the 21% group. In one protocol the diet was discontinued at age 40 days and the rats were studied at age 80 days. In these rats all parameters of renal size and function were the same as in the rats that had had a normal (21%) protein intake from weaning. We conclude that in young rats high protein intake reversibly increases GFR out of proportion to BW and selectively and reversibly stimulates kidney growth by stimulating cell proliferation.     

Influence of different protein intake on renal growth in young rats

We have examined the effect of high protein intake on kidney growth and function in growing rats. The rats were kept on an isocaloric diet containing 12%, 21% and 50% protein, from weaning (16 days) until the time of investigation (18, 20, 24, 40 or 80 days). There was no significant difference between the 12% and 21% protein groups in any of the parameters studied. 50% protein increased body weight (BW) and kidney weight (KW). The increase in kidney weight was already evident after 2 days and exceeded the increase in body weight in all age groups. At 24 days renal cortical DNA and the protein/DNA ratio were significantly increased in the 50% protein group. At 40 days the cortical DNA content, but not the protein/DNA ratio, was significantly increased in the 50% group. The glomerular filtration rate GFR) was studied at 40 days. Total GFR as well as GFR/BW was significantly higher in the 50% group than in the 21% group. In one protocol the diet was discontinued at age 40 days and the rats were studied at age 80 days. In these rats all parameters of renal size and function were the same as in the rats that had had a normal (21%) protein intake from weaning. We conclude that in young rats high protein intake reversibly increases GFR out of proportion to BW and selectively and reversibly stimulates kidney growth by stimulating cell proliferation.     

Neonatal ovine adrenal cortical and medullary Cell H+ responses to ACTH and prostaglandin E(2)

The microphysiometric technique was used to evaluate 1- and 3-day-old lamb adrenal gland H+ production in response to ACTH or PGE(2). ACTH stimulated cortical, but not medullary H+ production; maximal H+ by combined cortical and medullary cells was greater than by cortical cells alone (p < 0.05). In contrast, the magnitude of the H+ response to PGE(2) was greater with medullary than with cortical cells alone or with cortical and medullary cells combined (p < 0.05). The H+ response to ACTH was greater in 3-day-old compared to 1-day-old lambs while the potency of PGE(2) was not different at the ages studied. We conclude that in neonatal sheep: (1) ACTH and PGE(2) are potentially important in adrenal regulation, and (2) paracrine communication appears to be functioning as has been shown for adults.     

Influence of age on compensatory renal growth in rats

Rats were nephrectomized (nx) or sham-operated (s) at the age of 5 days (young) or 55 days (adult). Nx and s rats from the same litters were studied at various times 5-75 days after surgery with determination of kidney weight and of renal cortical DNA and protein content. In some protocols protein and DNA content were determined in a more homogeneous population of proximal tubular cells. In s rats body weight, kidney weight, renal cortical DNA content, and protein/DNA ratio increased until at least 80 days of age. Body growth was the same in nx and s rats. In young nx rats the remnant kidney was significantly enlarged 5 days after surgery. The difference in kidney size between nx and s rats increased continuously at least until the age of 80 days. The remnant kidney was 125 +/- 9% enlarged 3 wk after nx and 175 +/- 18% enlarged 8 wk after nx. Five days after nx there was no increase in cortical DNA content but a significant increase in protein/DNA ratio. From 2 wk after nx on, the DNA content was significantly higher in nx than in s rats but the protein/DNA ratio was the same in nx and s rats. In adult nx rats, the remnant kidney was enlarged to the same extent 3 and 8 wk after surgery (130 +/- 7 and 132 +/- 8%, respectively). The increase in kidney weight 8 wk after nx was significantly smaller in adult than in young rats. The cortical DNA content and protein/DNA ratio were both moderately but significantly increased in adult rats 8 wk after nx. In conclusion this study has established age-dependent differences regarding the degree, the nature and the duration of compensatory renal growth.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies of the immaturity of the ADH-dependent cAMP system in conscious newborn piglets--possible impairing effects of renal prostaglandins

In 24 conscious newborn piglets the effects of 20 micrograms/kg body weight IV 1-deamino-8-D-arginine-vasopressin (DDAVP) in group 1, 5 mg/kg PO indomethacin in group 2, and the combined effects of both drugs in group 3 were studied by measuring urinary flow rate, urinary osmolality, creatinine clearance, total urinary and nephrogenous cyclic-adenosine 3':5'-monophosphate (cAMP) excretion, medullary cAMP content, and renal prostaglandin (PG)E2 and PGF2 alpha, excretion. DDAVP alone had no significant effects on ther above parameters, whereas indomethacin alone reduced only the PG excretion significantly. When both drugs were administered simultaneously, urinary concentration increased significantly (urinary flow rate decreased from 2.4 +/- 0.4 to 1.4 +/- 0.3 ml/hr (means +/- S.E.), and urinary osmolality increased from 444 +/- 29 to 552 +/- 33 mOsm/liter). Total urinary and nephrogenous cAMP excretion increased from 590 +/- 48 to 854 +/- 78 and 302 +/- 36 to 590 +/- 81 pmoles/hr/g kidney weight, respectively, whereas PGE2 and PGF2 alpha decreased from 249 +/- 33 to 19 +/- 4 and 192 +/- 32 to 43 +/- 7 pg/hr/g kidney weight, respectively. In addition, medullary cAMP content was considerably higher in group 3 (2010 +/- 200 pmoles/g medulla) than that observed in the control (1187 +/- 137), DDAVP (1218 +/- 115), and indomethacin (1230 +/- 168) groups.     

Effect of hypoxia on renal prostaglandin E2 production in human and rat neonates.

Effect of hypoxia on renal prostaglandin E2 (PGE2) production was shown in asphyxic newborn infants and experimental hypoxic rats. In asphyxic infants, at postnatal day 1, the urinary excretion of PGE2 in severe asphyxia (1.00 +/- 0.19 pg/kg/min, n = 10) was lower than that of the mild asphyxia (2.15 +/- 0.18 pg/kg/min, n = 10) or normal newborn infants (2.65 +/- 0.25 pg/kg/min, n = 8) (p less than 0.01). The urinary excretion of PGE2 was inversely correlated with the urinary N-acetyl-beta-D-glucosaminidase (r = -0.84, p less than 0.01). The urine volume in mild asphyxia (0.04 +/- 0.005 ml/kg/min) was higher in comparison to normal newborn infants (0.026 +/- 0.002 ml/kg/min) (p less than 0.01), but had no correlation with the urinary excretion of PGE2. In experimental hypoxic rats, the renal PGE2 concentration increased from 0.19 +/- 0.02 ng/mg protein to the maximum level of 0.59 +/- 0.03 ng/mg protein at 10 min of hypoxia. The renal PGE2 concentration then decreased to the minimum level (0.105 +/- 0.02 ng/mg protein) at 24 h after 20 min hypoxia. The renal ATP rapidly decreased during 20 min hypoxia, and gradually increased to 55.1 +/- 6.2 nmol/mg protein at 24 h after 20 min hypoxia, which recovered only about 60% of the control level. It seems likely that renal PGE2 does not play a major role in diuresis in mild birth asphyxia and that severe birth asphyxia suppresses the renal PGE2 production in early neonatal period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis of prostaglandins and lipoxygenase products by rat glomeruli during development

In glomeruli isolated from adult rats, arachidonic acid (C20:4) is metabolized through at least two different pathways: the lipoxygenase and the cyclooxygenase pathway, resulting in the synthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) and four prostaglandins (PG) respectively. Because renal blood flow (RBF) and glomerular filtration rate (GFR) increase during development, and because C20:4 metabolites are implicated in their local regulation, the conversion of 3H-C20:4 was studied in 3 groups of rats; group A: 4 days old, 10 g; group B: 10 days old, 25 g; group C: 60 days old, 200 g. Glomeruli mechanically isolated from blanched kidneys were incubated with 5.4 X 10(-8) M 3H-C20:4. Lipoxygenase and cyclooxygenase products were extracted and resolved by high-performance liquid chromatography (HPLC); quantitative determination of PGs was performed by radioimmunoassay (RIA). The results are: (1) conversion of C20:4 to lipoxygenase product is predominant in comparison to cyclooxygenase products; (2) conversion of labeled C20:4 into 12-HETE is constant with age; (3) identified cyclooxygenase products, PGE2, and particularly PGF2 alpha are maximum in group B; (4) the variation of C20:4 metabolism during development suggest that these products may be involved in the maturation and the regulation of glomerular functions.     

Mechanisms for colonic sodium transport during ontogeny: loss of an amiloride-sensitive sodium pathway

Net colonic sodium and fluid absorption is higher in suckling and weanling rats than in adult rats. This study was undertaken to investigate the mechanisms behind these differences. In vivo perfusion of the colon was performed in 14- to 80-day-old rats. Net Na and water uptake decreased exponentially from 14 to 80 days of age. Na uptake was 402 +/- 73 micrograms Eq/min/g DT in 20-day-old rats and 116 +/- 6 mu Eq/min/g DT in 40-day-old rats. After amiloride treatment, net Na transport was reversed to net secretion (-79 +/- 36 mu Eq/min/g DT) in 20-day-old rats. Amiloride had no effect on the net Na transport in 40-day-old rats. cAMP stimulation significantly increased the net Na uptake in 20-day-old rats and significantly reduced the net Na uptake in 80-day-old rats. cAMP did not increase the net uptake in amiloride-treated 20-day-old rats. We conclude that there are both quantitative and regulatory changes in the pathways for colonic Na transport during development, and we speculate that the large amiloride-sensitive sodium uptake in the young colon is adaptive and contributes to the sodium accretion necessary for rapid growth during late postnatal development.     

Chronic partial ureteral obstruction in the neonatal guinea pig. II. Pressure gradients affecting glomerular filtration rate

Neonatal guinea pigs with chronic partial ureteral obstruction (CPUO) and contralateral nephrectomy develop hydroureteronephrosis and reduced glomerular filtration rate (GFR) without significant reduction of renal blood flow. To investigate the role of pressure gradients in determination of GFR, micropuncture studies were performed in animals 23 +/- 3 days of age subjected to left ureteral constriction and right nephrectomy within the first 2 days of life and compared to uninephrectomized controls. Resulting ureteral dilatation was variable, with kidney weight and ureteral diameter being proportional to the rise in ureteral pressure (PU). In individual animals with severe CPUO (ureteral diameter greater than or equal to 3 mm), distal tubular transit time was either normal (31-90 s) or prolonged (greater than 120 s). Superficial single nephron GFR (SNGFR) was inversely correlated with PU. Glomerular capillary pressure and afferent arteriolar colloid oncotic pressure were not affected by CPUO while peritubular capillary, proximal and distal intratubular hydrostatic pressure increased as a function of PU. As a result, afferent effective filtration pressure (EFPA) was reduced in severe (10.0 +/- 1.1 mm Hg) compared to mild CPUO (13.4 +/- 0.5 mm Hg), but was not different from controls (11.3 +/- 0.9 mm Hg). For both control and CPUO groups, superficial SNGFR increased by 0.5 nl/min for each mm Hg increase in EFPA but for a given EFPA, SNGFR was 6 nl/min lower in guinea pigs with CPUO. These results indicate that higher EFPA in animals with mild compared to severe CPUO contributes to maintenance of higher SNGFR.(ABSTRACT TRUNCATED AT 250 WORDS)     

A micropuncture study of the development of renal function in the young rat.

Total kidney function and function of individual surface nephrons were measured under hypotonic saline load conditions in young rats 22-, 30- and 42-days old. The highest values of urine flow rate and GFR were found in 30-day-old rats. The water reabsorption was higher in 42-day-old rats than in two younger groups. This decreased fractional reabsorption of water in younger animals was detectable already in the late proximal tubule and in the early distal tubule. Fractional reabsorption of sodium was significantly lower at the age of 22 and 30 days than at the age of 42 days in both late proximal tubule and in the early distal one.     

Short-term effect of low and high protein intake on renal function in children with renal disease

The short-term effect of different levels of protein intake on renal function was investigated in 18 children with moderately (51-85 ml/min/1.73 m2 BSA) or severely (9-50 ml/min/1.73 m2 BSA) reduced glomerular filtration rates (GFR). The GFR and effective renal plasma flow (ERPF), estimated as the clearances of respectively inulin and para-aminohippuric acid during uncontrolled (2-2.5 g/kg bw), low (1.2 g/kg bw for 12 days) and high (3-5 g/kg bw for 24 h) protein intake were determined by a standard clearance method employing continuous infusion and spontaneous voiding. There were no significant differences in GFR or ERPF during uncontrolled and low protein intake. During high protein intake the GFR and ERPF increased significantly in patients with GFRs above 50 ml/min/1.73 m2 BSA and ERPFs above 150 ml/min/1.73 m2 BSA. It is concluded that these findings might indicate a functional reserve capacity in children with only moderately reduced renal function.     

Postnatal development of renal function in piglets: glomerular filtration rate, clearance of PAH and PAH extraction.

Glomerular filtration rate (GFR), estimated as clearance of inulin, and clearance of p-aminohippuric acid (CPAH) were measured in 32 unanaesthetized piglets 1--62 days of age. During this period of time, GFR increased from 0.27 to 0.59 ml/min/g kidney and CPAH increased from 1.02 to 1.72 ml/min/g kidney. At 8 weeks of age, GFR and CPAH equaled adult values. In addition, renal PAH extraction (EPAH) was estimated in 12 anaesthetized piglets aged 1--79 days. EPAH increased from 0.75 at birth to 0.86 (adult value) at 3 weeks of age. The result shows a postnatal increase in renal functions in piglets, but the development from birth to adult level was less pronounced than seen in other animal species.     

Prostaglandin-mediated effects on growth and markers of biochemical development in the rat

Several markers of growth and biochemical development in the rat were studied after administration of prostacyclin (PGI2) and 16, 16-dimethyl prostaglandin E2 (16, 16DM PGE2). Intermittent administration of PGI2 for 3 days to 10- and 19-day-old animals, with subsequent sacrifice at 14 and 23 days, resulted in significant dose related decreases in growth at 23 days. Total sucrase and maltase (glucoamylase) activities were elevated compared to controls at 14 days. Total activities of these enzymes were decreased in postweaned 23-day-old animals, but specific activities per mg intestinal protein were not significantly different. 16, 16DM PGE2 administered continuously between day 10-16 of life caused alterations in growth as well as increases in sucrase and maltase (glucoamylase) activities. Exogenously administered prostaglandins, therefore, are associated with altered growth and markers of biochemical development in the rat.     

Short-Term Effect of Low and High Protein Intake on Renal Function in Children with Renal Disease

ABSTRACT. The short-term effect of different levels of protein intake on renal function was investigated in 18 children with moderately (51–85 ml/min/1.73 m² BSA) or severely (9–50 ml/min/1.73 m² BSA) reduced glomerular filtration rates (GFR). The GFR and effective renal plasma flow (ERPF), estimated as the clearances of respectively inulin and para-aminohippuric acid during uncontrolled (2-2.5 g/kg bw), low (1.2 g/kg bw for 12 days) and high (3–5 g/kg bw for 24 h) protein intake were determined by a standard clearance method employing continuous infusion and spontaneous voiding. There were no significant differences in GFR or ERPF during uncontrolled and low protein intake. During high protein intake the GFR and ERPF increased significantly in patients with GFRs above 50 ml/min/1.73 m² BSA and ERPFs above 150 ml/min/1.73 m² BSA. It is concluded that these findings might indicate a functional reserve capacity in children with only moderately reduced renal function.     

先天性肾积水患儿肾脏水通道蛋白表达与肾实质厚度和肾小球滤过率的相关性

目的：探讨先天性肾积水患儿肾脏水通道蛋白AQP1-4 的表达与肾实质厚度和肾小球滤过率（GFR）变化之间的关系。方法：利用Western blot检测AQP1-4蛋白在10例先天性肾积水患儿(年龄62.3±18.3个月)10个肾组织和6例来自肾母细胞瘤手术切除患儿的正常肾脏组织(年龄62.7±17.1个月)中的相对表达量。同时对患侧肾脏肾实质厚度和GFR进行评估。积水肾脏AQP1-4表达与GFR以及肾实质厚度之间进行Pearson相关分析检验。结果：肾积水组AQP1-4蛋白相对表达均明显低于正常组（P＜0.05）。B超测量术前积水侧肾脏肾实质厚度平均为4.59±2.25 mm。99mTc-DTPA 测定积水侧肾脏GFR较对侧肾脏明显下降（40±12 mL/min vs 105±20 mL/min, P＜0.05）。积水组肾脏中AQP1-4蛋白相对表达量与肾实质厚度之间呈正相关,与患侧肾脏GFR之间亦呈正相关。积水侧肾脏肾实质厚度与GFR之间呈正相关。结论：先天性积水患儿肾脏AQP1-4蛋白表达下降,其表达量与肾实质厚度和肾脏GFR的变化呈正相关。     

Perinatal management of a preterm neonate affected by hyperprostaglandin E2 syndrome (HPS)

BACKGROUND: Neonates affected by hyperprostaglandin E(2) syndrome (HPS) present with severe polyuria. Both urinary losses as well as prostaglandin synthesis inhibitors may precipitate acute renal failure (ARF). AIM: Our goal was to maintain euvolaemia by replacement of urinary losses. PATIENT: Our patient was born prematurely with a family history typical of HPS. Urinary salt and water losses and PGE(2) excretion were determined in 2- to 4-h intervals. Salt and water were replaced accordingly. RESULTS: Within the first 48 h, urinary losses and PGE(2) increased continuously to 50 ml/kg/h and 374 ng/h/1.73 m(2), respectively. Following exposure to 0.05-0.5 mg/kg/d indomethacin, urinary output decreased steadily to 10-15/ml/kg/h.CONCLUSION: In euvolaemic preterm neonates with HPS and the need for excessive replacement of salt and water, inhibition of renal PGE(2) excretion with indomethacin effectively reduces polyuria and natriuresis without acutely compromising renal function.     

Estimated one-yr glomerular filtration rate is an excellent predictor of long-term graft survival in pediatric first kidney transplants

Acute rejection episodes following pediatric renal transplantation have been progressively reduced by recent immunosuppressive regimens. Nevertheless, grafts continue to fail over time and surrogate parameters for long-term RGS are lacking. We investigated post-transplant renal function within the first yr as an independent predictor of long-term RGS in 104 pediatric first kidney transplant recipients (mean age 11.1 +/- 3.9 yr; mean follow-up 8.3 +/- 3.5 yr) transplanted between January 1989 and December 2000. GFR was assessed by use of the Schwartz formula at 30 days and six and 12 months after transplantation, respectively. Patients were further stratified at all times according to GFR: (i) GFR<45 mL/min/1.73 m(2), (ii) GFR 45-80 mL/min/1.73 m(2), and (iii) GFR>80 mL/min/1.73 m(2). Cox regression analysis including factors potentially influencing long-term RGS, e.g., age, gender, transplant yr, HLA-mismatch, underlying renal disease, clinical acute rejection, absolute GFR as well as the change in GFR within the first yr was performed. Graft failure occurred in 24 out of 104 patients (23%) 6.2 yr (mean) after transplantation corresponding to a cumulative five-yr graft survival of 87.5%. GFRs at 30 days and six and 12 months were significantly associated with long-term RGS in the univariate cox regression analysis (GFR at 30 days, p = 0.045; GFR at six months, p = 0.004; GFR at 12 months, p < 0.001). None of the other variables were significant parameters of correlation. Multivariate cox analysis revealed a GFR below 45 mL/min/1.73 m(2) at 12 months after transplantation as the only independent predictor of long-term RGS (hazard ratio 55.9, 95% CI 5.29-591, p = 0.001). GFR at 12 months post-transplant is an excellent surrogate parameter for long-term RGS in children. This parameter might be useful as a primary end-point in short-term pediatric clinical trials.     

Age-related differences in acute physiologic response to focal traumatic brain injury in piglets

INTRODUCTION: The goal of the present study was to determine whether age-related differences in the acute physiologic response to scaled cortical impact injury contribute to differences in vulnerability to traumatic brain injury (TBI). METHODS: Heart rate (HR), mean arterial pressure (MAP), brain temperature (BrT) and cerebral blood flow (CBF) were measured in 22 piglets (7 of age 5 days, 8 of age 1 month, 7 of age 4 months) at baseline and for 3 h following scaled cortical impact injury. RESULTS: There were no age-dependent variations from baseline in HR, MAP or BrT following injury. CBF increased in the 5-day-old animals following injury while CBF in the 1- and 4-month-old animals decreased following injury (p = 0.0049). CONCLUSION: CBF was shown to have a significant age-dependent response to TBI with the youngest animals exhibiting increased CBF following injury.     

Gastrointestinal processing of gastrically administered prostaglandin F2 alpha in suckling and weanling rats

In view of the presence of prostaglandins in milk, studies were performed to determine if maturational differences are present in the gastrointestinal processing of exogenous prostaglandin F2 alpha. Suckling (10- to 14-day-old) and weanling (30-day-old) rats were gastrically fed 3H-labeled prostaglandin F2 alpha and killed 2 h later. Characterization of radioactivity present in the stomach from animals of both age groups revealed low prostaglandin F2 alpha metabolism. Analyses of proximal, middle, and distal intestinal segments revealed age-related differences in prostaglandin metabolism. The amount of unmetabolized PGF2 alpha in intestinal segments of suckling rats ranged from 11.4 to 13.5%. In weanling rats, there was a tendency toward increased amounts of intact PGF2 alpha in proximal (16.3 +/- 1.6%) and middle (17.6 +/- 2.2%) regions; however, 25.9 +/- 1.9% of the tissue radioactivity present in the distal small intestine of weanling rats was authentic PGF2 alpha, significantly greater than that of the distal segment of suckling rats. The intestine of weanling rats contained greater amounts of less polar metabolites. These results indicate that orogastrically fed prostaglandin can pass through the gastrointestinal tract of developing rats and be delivered to the distal intestinal mucosa intact.