The mechanism of the urinary concentrating defect in potassium deficient rats

Summary The mechanism of the defect in urinary concentrating capacity in potassium deficiency was investigated by measuring solute-free water reabsorption ( ) in normal and hypokalemic rats undergoing mannitol diuresis. Since potassium-deficiency markedly lowered glomerular filtration rate (GFR), was examined in normal rats whose GFR had been comparably reduced either acutely by aortic constriction or chronically by feeding a salt- and protein-free diet. By calculating the volume of filtrate delivered to the loop of Henle from the GFR and C _osm it was found that in normal rats was linearly related to volume delivery. At each level of volume delivery to the loop hypokalemic rats formed about half the normal amount of . Decreased solute delivery to the loop of Henle, therefore, cannot be the cause of the concentrating defect in hypokalemia. It is concluded, therefore, that the impaired concentrating capacity in potassium deficiency results from defective sodium transport in the ascending limb of Henle's loop, so that at any level of sodium delivery to the loop less sodium is transported into the medulla and therefore less is generated.

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Zusammenfassung Der Mechanismus der verminderten Harnkonzentrierung bei Kaliummangel wurde anhand der Bestimmung des rückresorbierten freien Wassers ( ) während Mannitoldiurese an normalen und hypokaliämischen Ratten untersucht. Da die glomeruläre Filtration der hypokaliämischen Ratten deutlich eingeschränkt war, wurde bei den normalen Tieren eine ähnliche Reduktion der glomerulären Filtration akut durch Constriction der Aorta und chronisch durch Fütterung einer NaCl- und Protein-freien Diät erreicht.Das in die Henlesche Schleife einströmende Primärharnvolumen wurde aus der glomerulären Filtration und der osmolaren Clearance (Cosm) berechnet. Das Konzentrationsvermögen ( ) erwies sich als lineare Funktion des in die Henlesche Schleife einströmenden Primärharnvolumens. In hypokaliämischen Ratten war das Konzentrationsvermögen ( ) verglichen mit dem in die Henlesche Schleife einströmenden Primärharnvolumen, im ganzen Bereich auf ungefähr die Hälfte eingeschränkt.Daraus wird geschlossen, daß die eingeschränkte Harnkonzentrierung bei Hypokaliämie durch verminderten Natriumtransport im aufsteigenden Schenkel der Henleschen Schleife verursacht wird, und zwar derart, daß von der in die Henlesche Schleife einströmenden Natriummenge ein geringerer Anteil ins Nierenmark transportiert wird und deshalb weniger gebildet werden kann.

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This work was supported in part by a grant from the Dallas Heart Association and in part by a training grant 5 TI HE 5469-04 from the National Institutes of Health, U. S. Public Health Service.

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Work performed as trainee of U. S. Public Health Service, grant 5 TI HE 5469-04.     

Mouse models and the urinary concentrating mechanism in the new millennium

Our understanding of urinary concentrating and diluting mechanisms at the end of the 20th century was based largely on data from renal micropuncture studies, isolated perfused tubule studies, tissue analysis studies and anatomical studies, combined with mathematical modeling. Despite extensive data, several key questions remained to be answered. With the advent of the 21st century, a new approach, transgenic and knockout mouse technology, is providing critical new information about urinary concentrating processes. The central goal of this review is to summarize findings in transgenic and knockout mice pertinent to our understanding of the urinary concentrating mechanism, focusing chiefly on mice in which expression of specific renal transporters or receptors has been deleted. These include the major renal water channels (aquaporins), urea transporters, ion transporters and channels (NHE3, NKCC2, NCC, ENaC, ROMK, ClC-K1), G protein-coupled receptors (type 2 vasopressin receptor, prostaglandin receptors, endothelin receptors, angiotensin II receptors), and signaling molecules. These studies shed new light on several key questions concerning the urinary concentrating mechanism including: 1) elucidation of the role of water absorption from the descending limb of Henle in countercurrent multiplication, 2) an evaluation of the feasibility of the passive model of Kokko-Rector and Stephenson, 3) explication of the role of inner medullary collecting duct urea transport in water conservation, 4) an evaluation of the role of tubuloglomerular feedback in maintenance of appropriate distal delivery rates for effective regulation of urinary water excretion, and 5) elucidation of the importance of water reabsorption in the connecting tubule versus the collecting duct for maintenance of water balance.     

七氟烷对衰老模型大鼠认知功能的影响及机制初探

目的:探讨七氟烷(Sev)对衰老模型大鼠认知能力及大脑前额叶皮质炎症因子表达的影响.方法:48只4月龄雄性SD大鼠,于大鼠头颈部皮下注射D-半乳糖(125 mg·kg-1·d-1)持续42 d建立衰老大鼠模型,按随机数字表法分为4组:空白对照(Con)组、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体抑制剂M...     

当归多糖对衰老模型大鼠骨髓造血功能的影响及其机制

目的 探讨当归多糖（ASP）对衰老模型大鼠骨髓造血功能的影响及其机制。方法 6~8周雄性SD大鼠40只,随机分为正常组（n=10）、ASP正常组（n=10）、衰老模型组（n=10）和ASP衰老模型组（n=10）。药物注射完成第2天,取眼球血检测外周血常规,取股骨测定每根股骨骨髓单个核细胞（BMNCs）总数;CCK8测定BMNCs增殖能力;流式细胞术检测BMNCs增殖周期与活性氧簇（ROS）含量;造血祖细胞混合集落（CFU-Mix）培养检测BMNCs形成集落能力;衰老β半乳糖苷酶（SA-β-Gal）染色观察衰老BMNCs百分率;酶学法检测细胞总抗氧化能力（T-AOC）;Western blotting检测P53和P21蛋白表达;激光扫描共焦显微镜检测P53蛋白表达及定位。 结果 与衰老模型组比较,ASP衰老模型组外周血红细胞、血小板和白细胞总数下降得到抑制;股骨BMNCs细胞数升高;增殖能力提高;形成CFU-Mix数增加;SA-β-Gal染色阳性BMNCs百分率显著降低; G₁期细胞比例降低,S期细胞比例升高,细胞内ROS含量显著降低; T-AOC升高: P53和P21表达显著上调。 结论 ASP能延缓或拮抗D-半乳糖致大鼠骨髓造血细胞衰老,其机制可能与ASP抑制氧化应激,下调p53/p21通路有关。     

Mechanisms of impaired urinary concentrating ability in adult rats treated neonatally with enalapril

Neonatal angiotensin-converting enzyme inhibition or angiotensin II type-1 receptor blockade induces irreversible renal histological abnormalities and an impaired urinary concentrating ability in the rat. The aim of the present study was to determine the pathophysiological mechanisms underlying the defect in urine concentration in adult rats treated neonatally with enalapril. Male Wistar rats received daily intraperitoneal injections of enalapril (10 mg kg(-1)) or saline vehicle from 3 to 24 days of age. Assessments of fluid handling and maximal urine osmolality (Uosm(max)), renal function and tubular free water reabsorption (T(c)H2O) under pentobarbital anaesthesia, renal tissue solute concentrations, renal aquaporin-2 (AQP2) expression, and kidney histology, were performed in 12-16-week-old rats. Uosm(max) (1488 +/- 109 vs. 2858 +/- 116 mosm kg(-1), P < 0.05) and maximal T(c)H2O were reduced in enalapril- vs. vehicle-treated rats after administration of 1-desamino-8-D-arginine vasopressin. Neonatally enalapril-treated rats showed marked papillary atrophy, a decrease in medullary tissue solute concentrations, and a reduction in AQP2 expression specifically in the inner medulla. Glomerular filtration rate, renal plasma flow and urinary excretion rates of sodium, potassium and chloride did not differ between groups. In conclusion, adult rats treated neonatally with enalapril showed a urinary concentrating defect of renal origin which primarily could be explained by the papillary atrophy. However, an impaired ability to generate medullary interstitial hypertonicity, and a decrease in inner medullary AQP2 expression, also seem to contribute to this defect.     

Effect of magnesium deficiency on erythrocyte aging in rats

Rats placed on a magnesium-deficient diet show decreased erythrocyte magnesium concentration, shortened erythrocyte survival, and erythrocyte membrane ultrastructure defects and become progressively anemic. Whether these pathologic processes are due to abnormal erythropoiesis or occur in the peripheral circulation is unknown. In the present study, magnesium and hemoglobin concentrations, reticulocyte count, erythrocyte pyrophosphatase, and pyruvate kinase activities were determined at weekly intervals for 6 weeks in whole blood and age-dependent erythrocyte fractions isolated from inbred Fisher rats fed a diet deficient in magnesium or the same diet with added magnesium. Freeze-fracture electron microscopic examinations were performed on age-dependent erythrocyte fractions to evaluate the membrane defect. The youngest red cells from magnesium-deficient rats were similar to those of control animals with respect to erythrocyte magnesium concentrations, pyrophosphatase activities, and membrane morphology. The older erythrocyte fractions from magnesium-deficient rats showed significant decreases in magnesium concentrations, pyrophosphatase activity, and the presence of membrane abnormalities. Thus, new erythrocytes produced in magnesium-deficient rats appear to be normal but rapidly develop biochemical and morphologic abnormalities with aging in a magnesium-deficient plasma environment.     

骨髓间充质干细胞防护肾脏衰老的作用及其机制

背景：骨髓间充质干细胞具有分化成肾小管上皮细胞的功能,故推测,间充质干细胞可能具有治疗慢性肾功能减退的作用。 目的：研究骨髓来源的大鼠间充质干细胞防护肾脏衰老的作用及其可能的机制。 方法：实验建立衰老大鼠模型,尾静脉移植骨髓来源的大鼠间充质干细胞,应用荧光染料羟基荧光素二醋酸盐琥珀酰亚胺脂标记体外培养大鼠骨髓来源的间充质干细胞,将其回输肾脏衰老大鼠体内,应用荧光显微镜下观察间充质干细胞是否能够归巢于肾脏;全自动生化仪测定各组大鼠血清中尿素氮及肌酐水平变化;采用免疫荧光法,利用计算机图像叠加技术,观察蓝色荧光4’,6-二脒基-2-苯基吲哚分别与红色荧光的肾小管上皮细胞特异性蛋白-角蛋白的叠加情况。 结果与结论：骨髓来源的大鼠间充质干细胞能够归巢到衰老大鼠的肾脏。与衰老大鼠模型组相比,经过间充质干细胞生物治疗后的衰老大鼠血清中尿素氮及肌酐水平显著降低(P < 0.05),肾脏组织可见少量4’,6-二脒基-2-苯基吲哚及异硫氰酸荧光素标记的角蛋白双染阳性细胞。结果显示,骨髓来源的大鼠间充质干细胞通过向肾小管上皮分化,这可能是其改善衰老大鼠肾脏的机制之一。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

Effect of aging on ultrasonic vocalizations and laryngeal sensorimotor neurons in rats

While decline in vocal quality is prevalent in an aging population, the underlying neurobiological mechanisms contributing to age-related dysphonia are unknown and difficult to study in humans. Development of an animal model appears critical for investigating this issue. Using an established aging rat model, we evaluated if 50-kHz ultrasonic vocalizations in 10, 32-month-old (old) Fischer 344/Brown Norway rats differed from those in 10, 9-month-old (young adult) rats. The retrograde tracer, Cholera Toxin β, was injected to the thyroarytenoid muscle to determine if motoneuron loss in the nucleus ambiguus was associated with age. Results indicated that older rats had vocalizations with diminished acoustic complexity as demonstrated by reduced bandwidth, intensity, and peak frequency, and these changes were dependent on the type of 50-kHz vocalization. Simple calls of old rats had reduced bandwidth, peak frequency, and intensity while frequency-modulated calls of old rats had reduced bandwidth and intensity. Surprisingly, one call type, step calls, had increased duration in the aged rats. These findings reflect phonatory changes observed in older humans. We also found significant motoneuron loss in the nucleus ambiguus of aged rats, which suggests that motoneuron loss may be a contributing factor to decreased complexity and quality of ultrasonic vocalizations. These findings suggest that a rat ultrasonic phonation model may be useful for studying age-related changes in vocalization observed in humans.     

Effect of aging on striatal dopamine receptor subtypes in Wistar rats

Both D1 and D2 dopamine receptor subtypes are lost from striata as Wistar rats age. The magnitude of loss differs slightly for the two subtypes (approximately 30% for D1, approximately 40% for D2) as does the temporal pattern (progressive loss from 3 to 24 months for D2, no decrease in D1 after 12 months) although most D2 loss also occurs in the first half of the lifespan. Dopamine stimulated adenylate cyclase activity also declines during striatal aging in a manner roughly proportioned to D1 receptor loss.     

Effect of diet restriction on glucose metabolism and insulin responsiveness in aging rats

The effect of age and of prolonged caloric restriction on glucose tolerance and insulin responsiveness has been studied in male Fischer 344 rats. Beginning at 1 month of age dietary intake of an experimental group (R) was limited to 60% of that of the control group (AL) which was allowed to eat ad libitum. Studies were carried out at intervals up to 24 months of age. In AL rats the oral glucose tolerance curve showed progressively higher peak levels of plasma glucose with age, and a decrease in the plasma insulin concentration at the time of the glucose peak. The R group did not show the increase in peak value with age and the corresponding insulin concentration was lower than that of the AL group. These results are compatible with a delay in the first phase of insulin secretion in aging AL rats. Insulin-stimulated glucose disposal was assessed by the method of Reaven et al. [Diabetes, 32 (1983) 175], at ages 4, 12, 18 and 24 months; using infusions of 2 mU of insulin and 1 mg of glucose/min per kg, the steady-state plasma glucose level (SSPG) was slightly lower in R than in AL rats, while the steady-state plasma insulin level was reduced by 40-60%. In rats aged 18-24 months the hepatic glucose output, measured with [3-3H]glucose, was the same for AL and R rats in the basal state and was reduced to the same extent by insulin. In the presence of epinephrine and propranolol, infusion of glucose and insulin at various rates demonstrated that the plasma glucose clearance rate increased linearly with increasing SSPI, and at comparable SSPI levels was lower in R than in AL rats. The ability of insulin to stimulate glycogenesis from glucose was measured in primary hepatocyte cultures. Insulin increased glycogenesis 3-fold in cells from AL rats and 4-6-fold in cells from R rats. There was no effect of age. The increased insulin responsiveness of R rats was not due to an increase in insulin binding or to a decrease in insulin degradation (measured with intact cells or as cytosolic insulinase activity).(ABSTRACT TRUNCATED AT 400 WORDS)