Influence of variations in hydration and in solute excretion on the effects of lysine-vasopressin infusion on urinary and renal tissue composition in the conscious rat

1. The changes in urinary and renal tissue composition induced by continuous, intravenous infusion of lysine-vasopressin (60 mu-u./min. 100 g body wt. until steady-state conditions prevailed) in normally hydrated, hydropaenic, saline-loaded (0.9%, w/v) and mannitol-loaded (15%, w/v) rats were determined and compared with those induced in water-loaded rats.2. Previous reports that the urinary responses to antidiuretic hormones vary both with hydration status and with concurrent solute excretion rate were confirmed.3. The data show that variations in urinary responses were accompanied by differences in the papillary responses to lysine-vasopressin.4. The results are discussed in terms of the effects of hydration and concurrent solute excretion on factors influencing (a) medullary accumulation of water and solute, (b) osmotic water reabsorption and (c) osmotic equilibration across the collecting duct; and of the effects of lysine-vasopressin on these factors.5. It is concluded that the effects of hydration and solute excretion on the antidiuretic responses to lysine-vasopressin may be interpreted by differences in (a) the medullary composition prevailing at the start and (b) any further changes in medullary composition that can be induced under the experimental circumstances.     

The time course of changes in renal tissue composition during mannitol diuresis in the rat

1. The time course and extent of changes in the composition of renal tissue slices in osmotic diuresis were determined by sacrificing groups of rats before and during the intravenous infusion of mannitol (15 g/100 ml.) for up to 7½ hr.

2. Very rapid changes in tissue water and solute contents occurred within 15 min, preceding the times of maximal diuresis, with little subsequent change even up to 7½ hr.

3. The main changes were:

(a) an increase in water content in all slices, particularly the papilla; (b) a very profound decrease in papillary and medullary urea content in the first 15 min, with a small, but significant, further decrease, subsequently; (c) a small, but significant, rapid decrease in papillary sodium, and small non-significant increases in the outer medulla and cortex. Subsequent changes in any segment were small and non-significant; (d) apart from small changes in the first 15 min ammonium and potassium contents remained fairly constant.

4. The rates of change in papillary and urinary urea concentrations were similar, so that after 30 min, any differences between tip and urinary concentrations were small and non-significant.

5. The findings are discussed in terms of factors influencing counter-current mechanisms. It is concluded that altered medullary blood flow is mainly responsible for the rapid changes in medullary composition.

6. The relation between papillary and urinary urea concentrations is explicable in terms of passive handling, with equilibration across a freely permeable collecting duct membrane.

     

The time course of changes in renal tissue composition during water diuresis in the rat

1. The time course and extent of changes in the composition of renal tissue slices in water diuresis were determined by sacrificing groups of rats before and during the intravenous infusion of dextrose (2.5 g/100 ml.) in amounts sufficient to administer over 2 hr, and subsequently to maintain for up to 7(1/2) hr, a positive fluid load of 4% body weight.2. The corticomedullary osmolal gradient characteristic of the nondiuretic rats was progressively dissipated until, at 7(1/2) hr, only papillary tip concentrations were higher than those of other segments.3. The changes in individual constituents followed different time courses: (i) an increase in water content in all segments, particularly the papilla, was almost complete by 1 hr, preceding the maximal increases in urine flow; (ii) a marked decrease in papillary and medullary urea content in the first hour was followed by a slower, progressive decrease leading to an almost complete dissipation of the urea gradient by 7(1/2) hr; (iii) small, non-significant decreases in sodium content occurred in all segments in the first hr, followed by a further small, progressive decrease in papillary sodium content; (iv) changes in ammonium and potassium concentrations were mainly related to those in water content, since the contents of these solutes showed only small changes.4. By 2 hr, differences in the rates of decline of osmolal and urea concentrations in urine and papilla led to urinary concentrations significantly lower than papillary values. The steep papilla-urine urea concentration difference became smaller, but remained significant even at 7(1/2) hr.5. The findings are discussed in terms of changes in countercurrent mechanisms, particularly as influenced by anti-diuretic hormone.6. The development of papilla/urine urea concentration ratio greater than unity is also considered in terms of passive transport with changes in membrane permeability.     

Time course of changes in renal tissue and urinary composition after cessation of constant infusion of lysine vasopressin in the conscious, hydrated rat

1. The changes in urinary and renal tissue composition in conscious rats were determined for up to 2 hr following the cessation of intravenous infusion of lysine vasopressin, LVP (at 60 muu./min. 100 g body wt. for 4(1/2) hr). A constant water load (4% body wt.) was maintained during and after lysine vasopressin infusion, by quantitative replacement of excreted water. In these circumstances, any changes in urinary and renal tissue composition are presumed to represent direct consequences of the rapid plasma and tissue clearance of lysine vasopressin.2. Urinary flow increased and osmolality decreased, rapidly, reaching stable values characteristic of sustained water diuresis after about 60 min.3. The steepness of the corticomedullary solute concentration gradients also decreased rapidly. Papillary Na and urea concentrations fell to values characteristic of sustained water diuresis in about 45 min.4. The changes in medullary composition were compounded of a moderate significant increase in water content, a moderate, significant decrease in Na content, and a profound decrease in urea content.5. In the eventual steady-state water diuresis, urinary outputs of Na and K were significantly lower, and of NH(4) significantly higher, than those observed in control experiments where LVP infusion was continued for the corresponding 2 hr.6. It is concluded that the diuresis following the cessation of LVP infusion is due not merely to reduced nephron permeability to water but also to a rapid reduction in the osmotic force responsible for water reabsorption from the collecting duct.     

Influence of prehydration on the changes in renal tissue composition induced by water diuresis in the rat

1. The composition of renal tissue was determined in rats before and immediately after intravenous infusion of dextrose (2.5 g/100 ml.) in amounts sufficient to administer a positive fluid load of 4% body weight over 2 hr. The rats were classified into three groups, according to the preinfusion urine osmolality: hydropaenia, normal and moderately diuretic (over 2400, 800-1500 and below 800 mu-osmoles/g H(2)O, respectively).2. In non-infused rats, the steepness of the corticomedullary osmolal gradient varied, due to differences in both water and solute (sodium and urea) contents, and was related to urinary osmolality. Whereas differences in medullary and papillary solute contents occurred between all three groups, papillary water content was significantly higher only in the moderately diuretic animals.3. Dextrose infusion caused the induction of water diuresis, the lowest urinary osmolalities being produced in the previously moderately diuretic animals.4. Dextrose infusion caused a considerable reduction in the steepness of the corticomedullary osmolal gradient in all rats, particularly in the previously hydropaenic animals, due to changes in both solute (sodium and urea) and water contents. Whereas reductions in medullary and papillary solute contents occurred in all three groups, there was no further increase in papillary water content from the already high values seen in the noninfused diuretic animals.5. Thus, dextrose infusion largely abolished any previous differences in tissue water content, whereas significant, though small, differences in osmolal (particularly urea) content persisted.6. These data are discussed in terms of changes and differences in endogenous antidiuretic hormone (A.D.H.) release.7. Changes in the magnitude and direction of the urinary-papillary urea concentration difference are discussed in terms of passive transport, with probable A.D.H.-induced changes in nephron urea permeability.     

Effects of 0·9% saline infusion on urinary and renal tissue composition in the hydropaenic, normal and hydrated conscious rat

1. Changes in water and solute outputs of hydropaenic, normal and hydrated conscious rats were determined during intravenous infusion (0.2 ml./min) of isotonic (0.9%) saline for 4 hr; renal tissue composition was determined before, and after 1 or 2 hr, infusion.2. In normal and hydrated rats increased excretion of water and sodium was such that urinary output matched intravenous input from about 2 hr. In hydropaenic rats, the diuretic and natriuretic response was much reduced; a retention of infused saline, equivalent to 15% body weight, occurred over 4 hr.3. A considerable increase in urea output and clearance, and a smaller increase in potassium and ammonium outputs, occurred in all groups.4. The corticomedullary osmolal gradients characteristic of non-diuretic rats were largely dissipated during saline infusion: by 1 hr in normal and hydrated rats, and by 2 hr in the hydropaenic group.5. These changes were ascribable mainly to an increase in tissue water content in all segments, particularly in the hydropaenic group; and to a profound decrease in urea content in all groups.6. Changes in tissue sodium content were smaller, and differed between segments and between the differently hydrated groups. A decrease in papillary content occurred in hydropaenic and normal groups and an increase in cortical and outer medullary content occurred in all groups.7. After 2 hr saline infusion, incomplete papillary-urinary osmotic equilibration was evident in all groups.8. These changes in medullary osmolality and in papillary-urinary osmotic equilibration preceded the maximal diuresis, and must contribute to the diuresis induced by saline infusion, as in water and osmotic diureses.     

The time-course of changes in renal tissue composition during lysine vasopressin infusion in the rat

Summary The corticomedullary osmolal gradient, largely dissipated by sustained water-diuresis, was progressively repleted by continuous i.v. ADH infusion (lysine-vasopressin, 15 mU/min/100 g body weight) in conscious rats for up to 41/2 hr.A marked increase in sodium content was essentially complete by 1/2 hr in the papillary tip; smaller, but more progressive increases occurred in the papillary base and inner medulla. Increases in medullary urea content occurred mainly in the first 21/2 hr, especially in the papillary tip. A progressive decrease in water content of all medullary segments was preceded by a significant papillary tip increase at 1/2 hr.Papillary tip-urine osmotic equilibration was slowly achieved after about 21/2 hr. The small, but significant, tip-urinary urea concentration difference of water diuresis was more rapidly replaced by a substantial difference in the reverse direction.It is concluded that the changes can be explained, adequately, by ADH-induced modifications in water and urea permeabilities of distal nephron segments and, possibly, by changes in inner medullary blood flow; that the evidence of direct ADH stimulation of sodium transport is inconclusive; and that there was no evidence of active urea transport.     

The time course of cardiovascular changes in lactation in the rat

1. Cardiovascular changes in lactating rats have been traced from the first day post-partum to the end of the third week of lactation. The pattern of changes showed three phases.2. Between days 1 and 5 of lactation there were sharp rises in both cardiac output and in the blood flow/g tissue for most organs, but little change in the distribution of the cardiac output.3. Between days 5 and 15 of lactation cardiac output remained steady. The blood flow to tissues actively involved in the body's response to lactation (mammary glands, liver, gastrointestinal tract) also remained at high steady levels, but the blood flow to other tissues declined due to a redistribution of the cardiac output away from them and towards the growing mammary glands and splanchnic organs.4. Between days 15 and 22 of lactation there were further rises in both cardiac output and in the blood flow/g tissue for most organs.5. It is suggested that the increases in organ blood flows that occurred in the first few days after parturition (days 1-5) and at the end of lactation (days 15-22) were largely dependent on increases in cardiac output and may represent the maternal response to rapidly rising demands from the young at these times.     

Acute effects of lysine vasopressin injection (Single and continuous) on urinary composition in the conscious water diuretic rat

Summary ADH (synthetic lysine-vasopressin) was administered to conscious rats undergoing steady, sustained water diuresis. The magnitude and duration of the transient antidiuresis induced by single i. v. ADH injection (0.5–8 mU/100 g body weight) increased with the dose to a maximum urinary osmolality of 630 -osmole/g H₂O (returning towards control values within 1 hr).Both the magnitude of, and the time to attain, a stable antidiuretic effect with continuous i.v. ADH infusion (2.5–30 U/min/100 g body weight) varied with the dose. The maximal osmolality with 15 was almost as high as that with 30 U/min/100 g body weight (1815 and 1928 -osmole/g H₂O), but took longer to attain (4 and 2 hr, respectively).With both single and continuous ADH injection, a variable, inconsistent natriuresis and kaluresis occurred; the peak natriuresis preceded the time of maximal urinary osmolal and Na concentrations.The data are discussed in relation to (a) physiological rate of secretion of endogenous ADH and (b) the mechanisms responsible for the natriuresis.It is concluded that the natriuretic effect of ADH has little physiological significance in salt regulation.     

Influence of renal nerves on renin secretion in the conscious dog

In order to evaluate the influence of renal nerves on renin secretion during changes in blood volume, we studied the mean arterial blood pressure (MAP) and the renal venous plasma renin activity (PRA) in 6 conscious dogs having one intact and one denervated kidney.After a passive head-up tilt PRA increased significantly in the vein of the intact kidney while it remained stable in the denervated one.The intravenous injection of Furosemide (3 mg/kg) induced a rapid elevation of PRA in both renal veins. The kinetics of the variations of renin secretion were similar in the two kidneys, but its magnitude was significantly lower in the denervated side.After a slow hemorrhage of 2, 4 and 6 ml/kg, MAP was unchanged and PRA increased in both renal veins but in a significantly lower degree in the denervated side. When blood loss reached 8 ml/kg, MAP decreased and PRA increased identically in the two renal veins.It was concluded that, in conscious dogs, the renal nerves could participate in the rapid adaptations of renin secretion during small changes in the circulating blood volume.     

大鼠IgA肾病模型肾脏变化分析

目的探讨IgA肾病(IgA nephropathy,IgAN)大鼠肾小体、肾小囊、肾小球和近端肾小管病理变化。方法将20只SD雌性大鼠随机分成2组,即对照组和IgAN组(n=10)。用免疫荧光、HE染色和体视学方法,测出2组动物肾小体、肾小囊和肾小球体密度、球囊体积比、肾小体数密度、肾小体和肾小球长径、近端肾小管管腔和管壁面积及其比值,比较其差异。结果IgA免疫荧光染色,IgAN组皮质部见较强绿色荧光。与对照组比,IgAN组肾小体体密度增大,肾小囊体密度增大,肾小球体密度减小,球囊比减小,肾小体数密度变化差异无显著性,肾小体长径增大,肾小球长径减小,近端肾小管管腔面积减小,管壁面积增大,腔壁比减小。结论 IgAN大鼠肾小体和肾小囊增大,肾小球减小,近曲小管细胞体积增大,管腔变小。     

Analysis of the changes of renal tissue in the rat model of IgA nephropathy

目的 探讨IgA肾病(IgA nephropathy,IgAN)大鼠肾小体、肾小囊、肾小球和近端肾小管病理变化.方法 将20只SD雌性大鼠随机分成2组,即对照组和IgAN组(n=10).用免疫荧光、HE染色和体视学方法,测出2组动物肾小体、肾小囊和肾小球体密度、球囊体积比、肾小体数密度、肾小体和肾小球长径、近端肾小管管腔和管壁面积及其比值,比较其差异.结果 IgA免疫荧光染色,IgAN组皮质部见较强绿色荧光.与对照组比,IgAN组肾小体体密度增大,肾小囊体密度增大,肾小球体密度减小,球囊比减小,肾小体数密度变化差异无显著性,肾小体长径增大,肾小球长径减小,近端肾小管管腔面积减小,管壁面积增大,腔壁比减小.结论 IgAN大鼠肾小体和肾小囊增大,肾小球减小,近曲小管细胞体积增大,管腔变小.     

The time course of thyroid-hormone-induced changes in the isotonic and isometric properties of rat soleus muscle

Rat thyroidectomy resulted in changes in a number of parameters used to characterise the mechanical and histochemical status of skeletal muscle. Thus thyroidectomy resulted in a prolongation of soleus slow-twitch muscle isometric contraction time and half-relaxation time with a reduced maximum velocity of shortening and maximum rate of development of tetanic tension but no significant change in twitch: tetanus ratio i.e. the ratio of twitch force/unit area to tetanic force/unit area. In addition the percentage of IIA fibres was reduced and the percentage of type I fibres increased. Triiodothyronine, administered to hypothyroid rats, brought about a speeding of these parameters again with no change in twitch: tetanus ratio. There was an increase in the percentage of IIA fibres with a concomitant reduction in the percentage of type I fibres. These changes were induced over 18 days and resulted in isotonic and isometric properties almost identical to those of soleus muscles from chronically hyperthyroid rats; speeding could be detected as early as 2 days after triiodothyronine had been given. Consideration is given to the possibility that changes in myosin isoforms and/or the kinetics of changes in intracellular calcium concentration in activation and relaxation could account for the time course of the observed changes.     

百令对慢性肾衰竭模型大鼠肾脏保护和肾结缔组织生长因子表达的影响

目的 观察百令对5/6肾切除大鼠的肾脏保护作用及对肾结缔组织生长因子(CTGF)表达的影响,探讨其延缓肾衰竭进展及抗纤维化的相关机制. 方法 50只SD大鼠随机取8只为假手术组,其余行5/6肾切除术.根据术后3周血肌酐(Scr)值分为模型组、天然虫草组(2.0 g·kg-1·d-1)、百令治疗组(2.0 g·kg-1·d-1)和百令高剂量组(3.0 g·kg-1·d-1).术后4周给药.治疗1个月后检测Scr、尿素氮(BUN)浓度;光镜下观察肾脏病理改变,免疫组化方法检测肾组织CTGF、α平滑肌肌动蛋白(α-SMA)的表达水平,采用图像分析系统进行定量分析. 结果 治疗后模型组大鼠Scr、BUN明显高于假手术组(P<0.01),肾小球与肾小管间质均有明显病理改变,CTGF、α-SMA的表达明显上调;而药物治疗组的Scr、BUN明显低于模型组(P<0.05),肾脏病理损伤减轻,CTGF、α-SMA的表达降低(P<0.05). 结论 百令能改善5/6肾切除大鼠的肾功能,减轻肾脏病理损害,其机制可能与下调肾组织CTGF的表达有关.     

Dissociation between changes in renal nerve activity and renal vascular resistance in conscious dogs

The effects of acute volume expansion and hemorrhage on renal nerve activity and renal vascular resistance were examined in chronically instrumented conscious dogs. In six conscious dogs, when the blood volume was expanded by 18 ml/kg, the mean arterial pressure increased by 14 +/- 3 mmHg, mean left atrial pressure increased by 5.3 +/- 0.7 mmHg, and renal nerve activity decreased by 87 +/- 3%, while the renal blood flow was not altered significantly and renal vasoconstriction occurred, i.e., the calculated renal vascular resistance increased by 12 +/- 4% from 0.49 +/- 0.05 mmHg/ml/min. Volume depletion, induced by 20 ml/kg hemorrhage, did not alter the mean arterial pressure (-4 +/- 6 mmHg), while it decreased the mean left atrial pressure by 4.0 +/- 0.7 mmHg and increased the renal nerve activity by 200 +/- 67%. However, the renal blood flow was well maintained at the pre-hemorrhagic control level and renal vasoconstriction did not occur. Thus, in conscious dogs, acute volume changes altered the renal nerve activity dramatically, but these changes in renal nerve activity did not exert any significant effects on renal vascular resistance.     

The time course of changes in contraction kinetics during the tonic activation of the rat tracheal smooth muscle

The tension increase after onset of electrical stimulation (30 Hz square wave; 1.65 ms pulse duration) and after the cessation of inhibiting length vibration (frequency 100 Hz sinus; amplitude 6% of the muscle length) was analysed in the isolated rat tracheal smooth muscle. In the first experimental series, tonic contraction was interrupted by a 2 s vibration applied 4–256 s after a preceding stimulation. In the second series, the onset of force development was delayed by a long-term vibration stopping 6–258 s after the commencement of a simultaneously performed electrical stimulation. In both the experimental series tested, the time course of post-vibration tension recovery showed an initial fast and a subsequent slow component. The former reflects the kinetics of cross-bridge reattachment and the latter those of the normal actin-myosin interaction cycle. The time constants of both these components reached a minimum of 0.58±0.04 s (fast) and 3.49±0.28 s (slow component) when the vibration stopped 18 s after the start of stimulation. Both values increased to 1.29±0.15 s and 9.98±1.17 s after a preceding stimulation of 256 s. These changes in the time constants may reflect the slowing of cross-bridge action under prolonged contraction. Such variations in the time constants of post-vibration tension recovery occurred without any corresponding changes in the steady state tension developed after cessation of vibration. These results lend further support to the supposition that different mechanisms might control the rate and extent of smooth muscle contraction.     

Time course of the renal functional response to partial nephrectomy: measurements in conscious rats

Previous investigations into the functional responses of the surviving nephrons following reductions in renal mass have been performed largely in anaesthetized animals and have taken little account of how the compensatory changes develop with time. The present study has assessed a method for determining glomerular filtration rate (GFR) in unrestrained, uncatheterized, conscious rats (plasma disappearance of (99m)Tc-diethylenetriamene pentaacetic acid (DTPA)) and has used this method to document the time course of the changes in GFR over a 32 day period following uninephrectomy or 5/6 nephrectomy. Concurrent measurements of excretion rates and of the clearance of lithium (the latter being an index of end-proximal fluid delivery) provided information on changes in overall tubular function and segmental reabsorption. After uninephrectomy, the GFR of the remaining kidney (compared with that of a single kidney of sham-operated animals) increased maximally (by approximately 50%) within 8 days; after 5/6 nephrectomy, the increase in the GFR of the remnant kidney was maximal (at approximately 300%) within 16 days. Overall excretion rates of sodium and potassium were well maintained in partially nephrectomized animals throughout the period of study, while the excretion of water increased (by approximately 30% after uninephrectomy and by approximately 120% after 5/6 nephrectomy), partly as a result of the compensatory increases in GFR but mainly as a consequence of moderate (after uninephrectomy) or marked (after 5/6 nephrectomy) reductions in fractional reabsorption. During the early period after 5/6 nephrectomy, potassium excretion sometimes exceeded the filtered load, indicating net secretion. Lithium clearance data indicated that the changes in tubular function after 5/6 nephrectomy include a reduction in fractional reabsorption in the proximal tubule, whereas after uninephrectomy any such effect on the proximal tubule is minor and transient.     

Dose response and time course studies on superoxide dismutase as a urinary biomarker of carbon tetrachloride-induced hepatic injury in the Hanover Wistar rat

Previous studies have shown that the enzyme copper/zinc superoxide dismutase (SOD-1) is increased in the urine of rats with carbon tetrachloride (CCl₄)-induced hepatotoxicity. The present experiments aimed to investigate further the usefulness of urinary SOD-1 as a non-invasive biomarker of liver injury. Two investigations were carried out, a dose response study and a time course study. In the dose response study, rats were given a single dose of CCl₄ at 0 (control), 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40 and 0.80 ml/kg and urine samples collected from 12 to 36 h postdosing. In the time course study, rats were dosed at 0.80 ml/kg CCl₄ and urine sampled at 4, 12, 24 and 36 h postdosing. In both studies, the presence of SOD-1 in the urine was confirmed by Western blotting with an SOD-1 antibody. In the dose response study, serum SOD activity was elevated in all CCl₄-treated animals and urinary SOD-1 activity was increased 2.2 times at the lowest dose (0.10 ml/kg) and 60.4 times at the highest CCl₄ dose level (0.80 ml/kg). In the time course study, urinary SOD-1 was first detected in samples collected from 4 to 12 h postdosing. We conclude that urinary SOD-1 has potential as a sensitive non-invasive biomarker of CCl₄-induced hepatocellular injury.