Antidiuretic hormone and renin in rats with diabetes insipidus

Administration of antidiuretic hormone to rats at a dose of 400 or 40 mu/100 g i.m. caused a significant fall in plasma renin concentration. (PRC). In male rats with diabetes insipidus, a significant elevation of both plasma and kidney renin concentrations was not significantly different from that in control female rats. Ovariectomy did not abolish this difference between female and male rats with hereditary diabetes insipidus. Plasma angiotensinogen (renin substrate) was significantly higher in male rats compared to females but no difference between rats with and without diabetes insipidus was observed.     

Impaired development of tolerance to morphine analgesia in rats with hereditary diabetes insipidus

Recently it was reported that vasopressin facilitates the development of resistance to the analgesic action of morphine. Therefore, the development of tolerance to daily administration of morphine-HCl (10 mg/kg i.p.) was studied in a series of trials on a hot plate using rats with hereditary diabetes insipidus (DI), which lack the ability to synthesize vasopressin. In contrast to heterozygous DI rats, who developed full tolerance after the fifth injection, homozygous DI rats showed a delayed development of tolerance. Substitution of HO-DI rats with either arginine-8-vasopressin (3 g/rat, s.c. daily) or the endocrinologically inert fragment of vasopressin desglycinamide lysine-8-vasopressin (5 g/100 g, s.c. daily) restored the impaired development of tolerance towards normal. The data support the notion that vasopressin is important to the development of tolerance to narcotic analgesics and that its mechanism of action is dissociated from its endocrine effect but rather resembles that of its known influence on memory consolidation.     

Vasopressin administration in the first month of life: Effects on growth and water metabolism in hypothalamic diabetes insipidus rats

Rats homozygous for the mutant gene for diabetes insipidus (Brattleboro strain) are stunted in growth compared to rats heterozygous for the mutant gene and normal rats without the mutant gene. The hypothesis was tested that normal growth depends upon the presence of vasopressin. It was expected that replacement therapy of vasopressin to rats homozygous for diabetes insipidus would make possible a normal growth rate similar to that of rats heterozygous for diabetes insipidus. Rats heterozygous and homozygous for diabetes insipidus were treated with 0.25 U (Days 0–9) and 0.5 U (Days 10–29) of vasopressin during the first month of life. During the treatment period, vasopressin significantly increased the urine osmolalities of the homozygous rats demonstrating the renal effectiveness of the vasopressin. The results showed that remedial vasopressin administration could not produce normal growth rates in homozygous rats and may be detrimental. Six weeks following vasopressin treatment, homozygous, diabetis insipidus rats which had received vasopressin had increased 24 hr water intakes and decreased urine osmolalities compared to control, homozygous rats. Heterozygous rats also had decreased urine osmolalities resulting from vasopressin six weeks after the cessation of vasopressin treatment.     

Suppression of drinking by naloxone in rats homo- and heterozygous for diabetes insipidus

The effects of the opiate antagonist, naloxone, alone and in combination with morphine, were examined on drinking induced by water deprivation in homo- and heterozygous Brattleboro rats manifesting an inherited diabetes insipidus. Both naloxone and a structurally-related congener, naltrexone (0.01–10 mg/kg), attenuated water consumption in adose-related fashion of 1 hr water-deprived homozygotes, which exhibit a complete absence of vasopressin. Drinking was also reduced by the two drugs in 24 hr water-deprived heterozygotes, which have detectable levels of vasopressin. Morphine pretreatment enhanced the antidipsogenic effects of naloxone in a dose- and time-dependent manner. The administration of 10 mg/kg of morphine 3 hr before testing, which itself did not affect drinking, maximally potentiated the suppressant effects of naloxone on drinking in homozygotes. This potentiating effect of morphine persisted for at least 48 hr. These results indicate that vasopressin is not essential for the antidipsogenic effects of the narcotic antagonists. The polydipsic Brattleboro rat may provide a convenient animal model for studies of the effects of opiate agonists and antagonists on drinking behavior.     

垂体瘤显微手术后尿崩的预防和治疗

目的 探讨垂体腺瘤术后尿崩症的预防和治疗,以减少术后尿崩的发生,提高垂体腺瘤手术的疗效.方法 回顾总结2012年8月至2015年8月本院神经外科显微手术治疗垂体腺瘤患者84例,26例肿瘤直径＞ 3cm向鞍上、鞍旁生长的巨大垂体腺瘤采用经额下人路显微手术摘除肿瘤,其余58例行单鼻孔蝶窦人路切除肿瘤,统计尿崩症的预防、发生和治疗情况.结果 84例患者术后出现尿崩35例(41.7％),其中26例巨大垂体腺瘤病例中发生尿崩19例(73.0％),其余58例垂体腺瘤病例术后发生尿崩16例(27.6％).经对症治疗,尿崩持续时间＜3周的21例,持续3周～3个月的12例,发生永久性尿崩的2例.结论 术前全面检查、充分准备,熟悉垂体后叶亮点的位置及肿瘤与周边组织的三维立体关系,术中避免损伤垂体、垂体柄、下丘脑及其供血血管,术后及时合理使用抗利尿药物与纠正水电解质平衡紊乱是预防和治疗垂体腺瘤术后尿崩症的关键.     

Lithium effects on citrate metabolism in humans and rats

Lithium treatment of manic-depressive patients was accompanied by decreased blood citrate, whereas lithium to rats led to increased blood citrate levels. The implications of these findings for urinary calcium excretion in lithium-treated humans and animals are discussed.     

鞍区肿瘤术后并发尿崩症的相关因素与护理

尿崩症是由于下丘脑垂体后叶通路受损导致的尿量增多、尿比重降低的临床综合征,是颅脑手术后、特别是鞍区肿瘤手术后常见的并发症,如不及时发现和处理,将影响病人术后恢复及生活质量,甚至危及生命。     

The renin and isorenin-angiotensin system in rats with hereditary hypothalamic diabetes insipidus

It is known that the active end product of the renin-angiotensin system, angiotensin II, will stimulate ADH release in the brain and corticosteroid release from the adrenal gland and it is possible that isorenin-angiotensin systems present in those tissues are important control mechanisms for that release. In these experiments plasma renin and adrenal gland and brain isorenin concentration (ISO-RC) measurements were made in rats of the Brattleboro strain with hereditary hypothalamic diabetes insipidus (DI) both with and without ADH substitution. Heterozygous DI rats have low storage levels of ADH but can maintain normal water balance. These animals had normal plasma renin concentrations and increased ISO-RC in the hypothalamus and neurohypophysis compared to Long-Evans control rats. Substitution with 100 mU ADH/day, given subcutaneously, decreased ISO-RC in both hypothalamic and neurohypophyseal tissues of heterozygous DI to control levels. In comparison with Long-Evans control rats, higher plasma renin concentrations and increased ISO-RC were found in adrenal gland and brain hypothalamus tissue of homozygous DI rats while no differences were observed in frontal cortex, medulla oblongata or choroid plexus. Substitution of homozygous DI rats with 100 mU ADH/day decreased plasma renin concentration but resulted in no correction of adrenal gland or brain ISO-RC. These results suggest the plasma renin-angiotensin system is altered by changes in fluid balance in the DI rat which can be corrected by ADH substitution. Changes in tissue ISO-RC in DI compared to controls are not related to fluid balance but may be correlated with brain ADH content.     

2型糖尿病大鼠超声心动图的变化

目的 探讨2型糖尿病(Type 2 diabetes mellitus,T2DM)大鼠超声心动图的变化及胰岛素对其的影响.方法 高糖高脂饮食加小剂量链脲佐菌素腹腔注射(STZ,30 mg/kg)制备T2DM大鼠模型,随机临床对照试验(randomized controlled trials RCT)分为正常对照组、糖尿病(Diabetes mellitus,DM)组和胰岛素治疗组(每只3 U/d股内侧皮下注射),对照组和DM组注射等剂量的生理盐水(股内侧皮下注射),每天1次,持续喂养2个月.结果 与对照组组比较,糖尿病模型组大鼠LVEDV、LVESV和SV均明显降低;其他有所增加(P＜0.05),胰岛素能显著降低LVFS、EF,对其他超声心动图指标无明显影响.结论 胰岛素能降低2型糖尿病大鼠的血糖,改善心功能,可不同程度下调SAN间质胶原的沉积.     

Lithium effects on serum calcium,magnesium and phosphate,in rats

Summary LiCl was injected daily to rats in a dose of 3 mmol/kg. The rats were, in different experiments, unoperated rats, parathyroidectomized rats and thyroparathyroidectomized rats.Serum concentrations of calcium, magnesium, and phosphate were measured 2 h after a lithium injection.Serum calcium was unaffected by lithium in unoperated and parathyroidectomized rats. In thyroparathyroidectomized rats lithium increased the serum calcium concentration.Serum magnesium was increased by lithium in all 3 groups of rats.Serum phosphate was slightly decreased by lithium in all 3 groups of rats.It is concluded that lithium increases both serum calcium and magnesium, but in the intact organism only a slight or no increase in serum calcium is seen after lithium due to physiological control mechanisms. After removal of the calcitonin producing C-cells in the thyroid gland the organism is unable to produce a fast decrease in serum calcium, and lithium is then able to increase the serum calcium concentration.     

Glucose transporters and insulin action: Some insights into diabetes management

Insulin stimulates glucose uptake in muscle and adipose cells primarily by recruiting GLUT4 from an intracellular storage pool to the plasma membrane. Dysfunction of this process known as insulin resistance causes hyperglycemia, a hallmark of diabetes and obesity. Thus the understanding of the mechanisms underlying this process at the molecular level may give an insight into the prevention and treatment of these health problems. GLUT4 in rat adipocytes, for example, constantly recycles between the cell surface and an intracellular pool by endocytosis and exocytosis, each of which is regulated by an insulin-sensitive and GLUT4-selective sorting mechanism. Our working hypothesis has been that this sorting mechanism includes a specific interaction of a cytosolic protein with the GLUT4 cytoplasmic domain. Indeed, a synthetic peptide of the C-terminal cytoplasmic domain of GLUT4 induces an insulin-like GLUT4 recruitment when introduced in rat adipocytes. Relevance of these observations to a novel euglycemic drug design is discussed.     

The Renal Handling of Lithium: Relation Between Lithium Clearance,Sodium Clearance and Urine Flow in Rats with Diabetes Insipidus

Abstract: In order to study the renal handling of lithium, I examined the relation between the lithium clearance and the urine flow in rats which had hereditary lack of vasopressin production and which had been given a test dose of lithium. The two variables were altered by varying the sodium intake. Rats with a low, medium and high sodium intake had a mean lithium clearance of 0.04, 0.22, and 0.40 ml/min./100 g body weight, respectively. When the sodium intake was increased from a medium to a high level, the lithium clearance and the urine flow rose in proportion to each other (r = 0.90). When the sodium intake was decreased from a medium to a low level, the lithium clearance fell relatively more than the urine flow so that the proportion between the two was changed. The experiments show that when vasopressin-induced alterations of the urine flow are excluded and when the sodium intake is not extremely low, proportionality may occur between the lithium clearance and the urine flow. This suggests that the lithium clearance varies in proportion to and is determined by the delivery of sodium from the proximal tubules.     

Attenuated arterial and venous constriction in conscious rats with streptozotocin-induced diabetes

We examined if arterial or venous constriction is impaired in early diabetes. Dose-pressor and mean circulatory filling pressure (index of venous tone) response curves to noradrenaline and angiotensin II were constructed in four groups of conscious, instrumented, Wistar rats pretreated with streptozotocin (60 mg/kg i.v.) or vehicle at 2 weeks prior to the study. Rats with diabetes, relative to controls, had increased ED(50) (reduced potency) for the pressor (2.5-fold of control) and mean circulatory filling pressure (4.3-fold of control) response to noradrenaline, as well as reduced maximum pressor response (efficacy) to noradrenaline (diabetic, 74+/-8 mm Hg; control, 96+/-5 mm Hg). Diabetic rats also had reduced potency (ED(50), 5-fold of control) of the pressor response to angiotensin II; however, maximum pressor response and dose-mean circulatory filling pressure curve to angiotensin II were similar in both groups. Therefore, arterial and venous constrictions are impaired at an early phase of type I diabetes.     

Central Effects of Lithium in Rats: Lithium Levels,Body Weight and Water Intake

Abstract: Male rats received LiCl for one week either by continuous intracerebroventricular injection from osmotic minipumps or by oral administration in the diet. Control groups received corresponding treatment with NaCl. The intracerebroventricular lithium treatment produced relatively high lithium levels in brain regions (0.6–2.3 mmol/kg) and negligible lithium levels in plasma (less than 0.1 mmol/l) while the oral treatment produced moderate lithium levels in brain regions as well as in blood (0.5–0.9 mmol/kg and 0.5–0.75 mmol/l, respectively). Body weight loss and enhanced water intake occurred in groups given oral lithium treatment as well as in those given lithium via minipumps. The results suggest that administration of lithium by minipumps may be of use to study central actions of lithium.     

91例颅咽管瘤术后并发症及预后分析

目的：探讨颅咽管瘤术后并发症发病机制及对预后的影响。方法选取中国医科大学附属第一医院2001年1月~2007年12月术后病理明确诊断的颅咽管瘤手术患者91例,统计术后常见并发症及预后不良患者的例数,探讨颅咽管瘤术后主要并发症的发病机制,统计分析其对预后的影响。结果91例患者中死亡8例,2例患者意识障碍较重,放弃治疗。21例患者术后出现程度不同的意识障碍,61例术后出现尿崩,59例出现水电解质紊乱,53例术后出现发热,4例出现术后癫痫发作。意识障碍与患者预后有相关性（P<0.01）。结论尿崩、水电解质紊乱、发热、癫痫等是颅咽管瘤术后常见并发症,往往伴有严重的意识障碍,成为影响颅咽管瘤预后的主要因素。     

Rescue of beta-cell exhaustion by diazoxide after the development of diabetes mellitus in rats with streptozotocin-induced diabetes

In this study, we attempted to demonstrate the possibility of rescuing beta-cell exhaustion by chronic intervention with an ATP-sensitive K(+) channel opener, diazoxide, which reduces the stress of insulin secretion, using rats with streptozotocin-induced diabetes. Three groups of male Wistar rats: (i) controls (n = 7), (ii) streptozotocin (30 mg/kg i.v.)-induced diabetic rats (n = 10), and (iii) streptozotocin-induced diabetic rats treated with diazoxide 30 mg/kg for 6 weeks (n = 10), were studied. Intraperitoneal 2-g glucose tolerance testing was performed every 2 weeks, and pancreatic tissue was examined after 6 weeks of treatment with diazoxide. The insulin concentration in diabetic rats treated with diazoxide was significantly higher than in diabetic rats without diazoxide (6.6 +/- 1.6 vs. 2.4 +/- 1.0 ng/ml, P < 0.05). The islet size and its cell number were reduced in diabetic rats compared to those in normal control rats. In normal control rats, 88% of pancreatic islet cells were insulin-positive, while 50% or less were positive in diabetic rats. However, islet size and its cell size appeared to be well preserved by diazoxide treatment. The average mass of islets in diazoxide-treated rats was significantly larger than that in untreated control animals. In addition, the degree of immunostaining for insulin was obviously higher in rats treated with diazoxide than in rats without diazoxide. Pancreatic proinsulin mRNA was restored in rats treated with diazoxide. The present study demonstrated that diazoxide protected from further damage the pancreatic beta-cells both functionally and morphologically in streptozotocin-induced diabetic rats by suppression of excessive insulin secretion. Our results strongly suggest the possibility that chronic intervention with an ATP-sensitive K(+) channel opener prevents the progress of deranged beta-cell function even after the development of diabetes mellitus.     

低渗造影剂对老年糖尿病大鼠肾毒性的研究

目的观察低渗造影剂欧乃派克350对老年糖尿病大鼠肾功能的影响。方法建立老年糖尿病大鼠模型,观察尾静脉注射欧乃派克350(10ml/kg)后,大鼠血肌酐、尿素氮以及肾组织匀浆一氧化氮(NO)、谷胱甘肽(GSH)的含量。结果老年糖尿病大鼠血肌酐、尿素氮与正常对照组比较均升高(P<0.05),肾组织匀浆一氧化氮、谷胱甘肽与正常对照组比较均下降(P<0.01,P<0.05)。注射造影剂后,血肌酐与正常对照组比较明显升高(P<0.01),肾组织匀浆一氧化氮与糖尿病对照组比较下降(P<0.05)。结论低渗造影剂可以引起老年糖尿病大鼠肾损伤,可能与糖尿病大鼠NO合成或消耗失调,进一步激活NO信号通路有关。     

The renal handling of lithium: relation between lithium clearance, sodium clearance and urine flow in rats with diabetes insipidus

In order to study the renal handling of lithium, I examined the relation between the lithium clearance and the urine flow in rats which had hereditary lack of vasopressin production and which had been given a test dose of lithium. The two variables were altered by varying the sodium intake. Rats with a low, medium and high sodium intake had a mean lithium clearance of 0.04, 0.22, and 0.40 ml/min./100 g body weight, respectively. When the sodium intake was increased from a medium to a high level, the lithium clearance and the urine flow rose in proportion to each other (r=0.90). When the sodium intake was decreased from a medium to a low level, the lithium clearance fell relatively more than the urine flow so that the proportion between the two was changed. The experiments show that when vasopressin-induced alterations of the urine flow are excluded and when the sodium intake is not extremely low, proportionality may occur between the lithium clearance and the urine flow. This suggests that the lithium clearance varies in proportion to and is determined by the delivery of sodium from the proximal tubules.     

Time course of lithium-induced alterations in renal and endocrine function in normal and Brattleboro rats with hypothalamic diabetes insipidus.

1. A lithium chloride (1.1 g/kg) supplemented diet was given to Long Evans (LE) and Brattleboro (DI) rats to investigate its actions in the presence (LE) and absence (DI) of vasopressin. 2. During the first 24 h, Li-supplemented LE rats displayed an initial water deficit (drinking less than renal output), increased plasma antidiuretic (ADH) titres and slightly increased plasma renin activities (PRA) and plasma osmolarities. Such changes were qualitatively similar to those seen in rats fed a normal diet, but deprived of water for 24 hours. After 12 days, the Li-supplemented rats had elevated plasma ADH titres, but reduced pituitary oxytocic and antidiuretic activities. 3. The urinary losses of Na, K and Cl exceeded dietary intakes in LE rats on the introduction of the Li-supplement, and the urinary osmolarity fell by 50%. Electrolyte balances were gradually re-established, although drinking and urine production increased in parallel to reach twice the control values by day 12 of the supplement. 4. Aldosterone and corticosterone secretory rates and their peripheral plasma concentrations were unchanged both after 24 h and 28 days of the Li-supplement. 5. Li elicited no water deficit or saluresis in DI rats, and although the polyuria and polydipsia were exacerbated, urinary osmolarity did not change over the 12 day observation period. 6. Li increased Ca excretion in both rat types; after 12 days the PRA of DI but not LE animals were increased. 7. It is concluded that the overall renal actions of Li are tempered by vasopressin rather than adrenocorticosteroids.