Glomerular barrier dysfunction in glomerulosclerosis- resistant Milan rats with experimental diabetes: the role of renal haemodynamics

Rats of the Milan hypertensive strain (MHS) are resistant to both hypertensive and diabetic renal disease. Genetically determined hypertrophy of intrarenal arteries has been suggested as the putative mechanism preventing transmission of systemic hypertension to the glomerular microcirculation or diabetes-induced loss of autoregulation, which lead to glomerular hypertension and consequent podocyte injury and proteinuria. This study aimed to investigate glomerular barrier function and structure in ageing and diabetic MHS rats under basal conditions and after injection of 2.5 g of bovine serum albumin (BSA) causing increased workload and possibly removing haemodynamic protection by inducing renal cortical vasodilatation. Genetically related rats of the Milan normotensive strain (MNS) served as a proteinuric counterpart. No change in renal function or structure was detected in diabetic MHS rats, whereas MNS rats developed diabetic nephropathy superimposed on that occurring spontaneously in this strain. Diabetic, but not non-diabetic, MHS rats showed significantly reduced synaptopodin and nephrin expression, though to a lesser extent than non-diabetic and diabetic MNS rats, together with unchanged podocyte number, density and structure and no proteinuria. Agrin expression was significantly altered in diabetic versus non-diabetic MHS animals, whereas collagen I was expressed only in diabetic MHS rats and collagen IV content did not change significantly between the two groups. Upon BSA injection, proteinuria increased markedly and abundant BSA was detected only in kidneys from diabetic MHS rats. BSA injection was associated with changes in intrarenal arteries suggesting vasodilatation, without any influx of inflammatory cells. These data indicate that while MNS rats show marked changes in the glomerular filtration barrier with either age or diabetes, glomerulosclerosis-resistant MHS rats develop only minor diabetes-induced podocyte (and extracellular matrix) alterations, which are not associated with proteinuria unless they are unmasked by an increased workload or removal of the haemodynamic protection.     

Age-dependent glomerulosclerosis and proteinuria occurring in rats of the Milan normotensive strain and not in rats of the Milan hypertensive strain

The development of an age-dependent glomerulosclerosis and proteinuria was investigated in two strains of rats in a model of moderate hypertension comparing rats of the Milan Hypertensive Strain (MHS) with rats of the Milan Normotensive Strain (MNS). Serum creatinine, urinary protein excretion, renal morphology (light- and electronmicroscopy) and morphometry of the media thickness of the intrarenal arteries and of the thickness of the glomerular basement membrane were studied in 2- to 16-month-old MHS and MNS rats. Serum creatinine did not differ between MNS and MHS rats in any age group. MNS rats developed a significant proteinuria which coincided with a glomerulosclerosis in about 22% of the glomeruli at 13 to 16 months. In contrast, urinary protein excretion in MHS rats remained stable during the entire observation period; glomerulosclerosis occurred only in 3% of the glomeruli at 13 to 16 months. As a consequence of hypertension media thickness of intrarenal arteries of MHS rats significantly exceeded that of MNS rats, in the interlobular arteries already at 2 months and in the arcuate arteries at 13 to 16 months. In contrast, thickness of the glomerular basement membrane of MHS rats never exceeded that of MNS rats. From these data we conclude, that glomeruli of MHS rats may be protected against the development of an age-dependent glomerulosclerosis and proteinuria. Further support for this conclusion may also be derived from recent experiments showing that the tubuloglomerular feedback sensitivity is significantly higher in MHS than in MNS rats (41).     

Renal hypertension following aortic constriction is abolished by angiotensin II converting enzyme inhibitor,but not by low-salt diet

This study evaluates the role of different sodium intakes and the role of angiotensin II in the development and the maintenance of renovascular hypertension in rats with constriction of the aorta proximal to the renal arteries. The rats were studied 3 weeks after surgery when the hypertension was well established. Glomerular filtration rate was decreased and filtration fraction was increased in rats with proximal aortic constriction. Low and high salt intakes had no effect on glomerular filtration and filtration fraction. Treatment with angiotensin II converting enzyme inhibitor increased the glomerular filtration rate and reduced the filtration fraction in rats with proximal aortic constriction to the same levels as in control rats. Serum levels of angiotensin II were about the same in rats with proximal aortic constriction as in control rats.     

Studies of the renal component of the hypertension in rats with aortic constriction. Role of angiotensin II

The object of this study was to investigate the renal component of hypertension in aortic constriction. In 40-day-old Sprague-Dawley rats the aorta were constricted either proximal (PAC) or distal (DAC) to the renal arteries. The rats were examined 3 weeks later together with control rats. The arterial pressure proximal to the constriction was elevated in the PAC group but not in the DAC group. In PAC rats the arterial pressure was also elevated distal to the constriction. There was a significant pressure gradient across the constriction in both PAC and DAC rats. The PAC rats had a significant decrease of renal blood flow, a significant increase in renal vascular resistance and a numerical but not significant decrease of glomerular filtration rate. Serum levels of angiotensin II were not significantly different in PAC and control rats. The pressor effect of a bolus dose of angiotensin II was significantly increased in PAC rats. Captopril, a converting enzyme inhibitor, decreased the arterial pressures and renal vascular resistance in PAC rats. The pressure elevating effects of angiotensin II and pressure lowering effect of captopril were more pronounced distal than proximal to the constriction. We conclude that the kidneys play a major role in the development of hypertension in PAC, and that the local effect of angiotensin II on the renal vascular bed is an important contributor to the renal component of the hypertension.     

ULTRASTRUCTURAL STUDIES ON GLOMERULAR LESIONS IN EXPERIMENTAL HYPERTENSION

Chronological and electron microscopic studies of glomerular lesions were carried out on four different experimental hypertension groups (renal hypertension by Goldblatt, adrenal regeneration hypertension, steroid-induced hypertension and salt hypertension) and two control groups (intact group and salt treated nonhypertension group).
There was no essential difference in glomerular lesions among the four different experimental hypertension groups, and It was understood that morphological changes were consequent to the experimental methods and hypertension. The thickening of basement membrane of capillary loop was proportional to the duration of hypertension and was in no way related to the onset of hypertension. The basement membrane was undoubtedly thickened even in intact rats due to aging. The thickening of basement membrane in nonhypertensive salt treated animals appeared earlier than that in the intact group. "Mesangial cell proliferation" observed In experimental hypertension groups contained a great number of monocytes from hematogenous source which entered into the intercellular space between mesangial cells and endothelial cells. Colliculus (cytoplasmic projection of mesangial cell) had no special relationship to the elevation of blood pressure but indicated important suggestions concerning renostimulating factors and mesangial cell function.     

肾血管性高血压时脑与肠系膜动脉壁CGRP能神经纤维分布的变化

目的：观察肾血管性高血压时中枢与外周动脉壁CGRP（calcitonin gene-related peptide）能神经纤维分布的变化,探讨CGRP与肾血管性高血压的关系.方法：应用免疫组织化学SABC法观察双肾双夹肾血管性高血压大鼠不同时期（术后4、8、12周）脑动脉壁和肠系膜动脉壁CGRP能神经纤维密度的变化.结果：高血压各组CGRP能神经纤维密度均高于对照组,有显著性差异（P＜0.01）;高血压组12周CGRP能神经纤维密度高于高血压组4周,有显著性差异（P＜0.01）;对照组CGRP能神经纤维较纤细,多沿血管长轴走行,高血压组CGRP能神经纤维较粗大,呈网状分布.结论：随着血压的升高,中枢与外周动脉壁CGRP能神经纤维密度增加,这可能是机体产生的一种代偿性保护机制,起着调节血压的作用.     

The morphology of the adrenals and kidney incretory structures in arterial hypertension

Glomerular and fascicular zones of the adrenal gland and the incretory renal structures of patients who had died from benign (20) and malignant (10) forms of essential hypertension, chronic glomerulonephritis (10) and of rats with a genetic hypertension (10) were examined by morphometric methods. Hypertrophy of glomerular and fascicular zones is observed in both forms of the hypertension disease, spontaneous hypertension and chronic glomerulonephritis. Correlation analysis revealed moderate and strong links between the volumes of nuclei and nucleoli; within each zone and between the zones. This may indicate an increased functional activity of the two zones and their close interaction. Factorial analysis revealed a sign indicator--nucleus volume of the glomerular zone cells. Numerous moderate and strong correlations between the incretory renal structures and the adrenal cortex in the malignant form of the hypertension disease may indicate not only the involvement of the renin-angiotensin-aldosteron- and prostaglandin-synthesizing systems in the pathogenesis of this disease but their interaction as well.     

Glomerular renin angiotensin system in streptozotocin diabetic and Zucker diabetic fatty rats

Substantial evidence suggests that the intrarenal renin-angiotensin system (RAS) plays a role in the pathogenesis of diabetic nephropathy. Although the glomerular RAS is activated in the streptozotocin (STZ)-diabetic rat, the status of the glomerular RAS in the Zucker diabetic fatty (ZDF) rat, which is a commonly used genetic model of diabetes, is not known. Angiotensinogen (AGT), angiotensin II (Ang II), angiotensin converting enzyme (ACE), and angiotensin converting enzyme 2 (ACE2) were measured in glomeruli isolated from 4-week-old STZ-diabetic rats and 32-week-old ZDF rats. Glomerular injury was evaluated by histopathologic methods. Both STZ-diabetic and ZDF rats exhibited marked hyperglycemia and renal hypertrophy, but only ZDF rats demonstrated proteinuria and glomerulosclerosis. Glomerular AGT and Ang II levels were increased significantly in STZ-diabetic compared with nondiabetic control rats, accompanied by a reduction in ACE2 activity. In contrast, glomerular AGT, Ang II, and ACE2 were similar in ZDF rats and lean controls. ACE levels were not affected by diabetes in either diabetic model. In conclusion, the glomerular RAS is activated in the STZ diabetic rat but not in the ZDF rat despite a similar degree of hyperglycemia. The mechanism of nephropathy in the ZDF rat may involve factors other than hyperglycemia and RAS activation, such as hypertension and hyperlipidemia.     

Acute arterial fibrinoid deposition and ischaemic parenchymal damage of the kidney. Pathogenic factors in the development of malignant hypertension

The development and evolution of hypertensive vascular lesions affecting the arterial supply of (a) the kidney and (b) organs other than the kidney were studied in rats developing either malignant (MHY) or benign (BHY) hypertension 3, 6, 9 and 12 days after aortic ligation between the renal arteries. Vascular disease evolved into two distinct patterns which suggested acute renal damage to be the determinant for the development of either the malignant or benign form of hypertension. Three days after aortic ligation MHY and BHY animals showed widespread fibrinoid deposition in vascular territories above the aortic ligature. However, in MHYs these lesions were much more severe and, in the kidney, they were accompanied by the development of focal parenchymal atrophy, microinfarcts and hyalin droplet degeneration of cells of the Bowman capsule. The degree of renal damage correlated with elevations in blood urea nitrogen (BUN) and plasma creatinine; however, there was no correlation with rises in blood pressure, plasma renin activity (PRA), aldosterone or corticosterone which were similarly elevated in 3-day MHY and 3-day BHY animals. Between 6 and 12 days a marked clearance of fibrinoid took place in all organ beds of BHYs, but in the non-renal vasculature of MHY animals fibrinoid remained prominent and served as the central core for necrotising arterial lesions. In the kidney of MHYs some reduction in the fibrinoid content was observed, but the parenchymal damage perpetuating from the earlier stages had exacerbated leading to collagen deposition and a marked increase in the collagen concentration of the renal cortex. These features were accompanied by further elevations in PRA and corticosteroids and a progressive deterioration of renal function. By contrast, in 12-day BHY animals, despite sustained hypertension, PRA and corticosteroids were falling from their previously higher levels and normal renal function was maintained. These studies warrant inference that extensive parenchymal damage of the kidney due in part to severe arterial fibrinoid deposition is one of the initial events in the development of malignant hypertension.     

Uteroplacental insufficiency causes a nephron deficit, modest renal insufficiency but no hypertension with ageing in female rats

In rats, uteroplacental insufficiency induced by uterine vessel ligation restricts fetal growth and impairs mammary development compromising postnatal growth. In male offspring, this results in a nephron deficit and hypertension which can be reversed by improving lactation and postnatal growth. Here, growth, blood pressure and nephron endowment in female offspring from mothers which underwent bilateral uterine vessel ligation (Restricted) on day 18 of pregnancy were examined. Sham surgery (Control) and a reduced litter group (Reduced at birth to 5, equivalent to Restricted group) were used as controls. Offspring (Control, Reduced, Restricted) were cross-fostered on postnatal day 1 onto a Control (normal lactation) or Restricted (impaired lactation) mother. Restricted-on-Restricted offspring were born small but were of similar weight to Control-on-Control by postnatal day 35. Blood pressure was not different between groups at 8, 12 or 20 weeks of age. Glomerular number was reduced in Restricted-on-Restricted offspring at 6 months without glomerular hypertrophy. Cross-fostering a Restricted pup onto a Control dam resulted in a glomerular number intermediate between Control-on-Control and Restricted-on-Restricted. Blood pressure, along with renal function, morphology and mRNA expression, was examined in Control-on-Control and Restricted-on-Restricted females at 18 months. Restricted-on-Restricted offspring did not become hypertensive but developed glomerular hypertrophy by 18 months. They had elevated plasma creatinine and alterations in renal mRNA expression of transforming growth factor-β₁, collagen IV (α1) and matrix matelloproteinase-9. This suggests that perinatally growth restricted female offspring may be susceptible to onset of renal injury and renal insufficiency with ageing in the absence of concomitant hypertension.     

Impairment and recovery of the clipped kidney in two kidney, one clip hypertensive rats during and after antihypertensive therapy

Earlier experiments have shown that in sodium depleted hypertensive rats with bilaterally constricted renal arteries the arterial pressure normalized after blockade of the renin-angiotensin system; simultaneously acute renal failure occurred. In hypertensive rats with unilateral renal artery stenosis an impaired excretory function of the clipped kidney can be expected, but may not be detectable by conventional tests of renal function. Male Wistar rats with chronic two kidney, one clip hypertension were fed a low sodium diet. After 7 days the rats were treated with vehicle, with the vasodilator dihydralazine, or with the angiotension converting enzyme inhibitor MK 421 for 2 weeks. During the 14-day treatment period a continuous blood pressure reduction was achieved in dihydralazine and MK 421 treated rats. Overall excretory kidney function (plasma creatinine concentration) was well maintained in all three groups until the end of the antihypertensive drug treatment. At the end of drug therapy mean glomerular filtration rates of the left clipped kidneys were significantly lower in both treated groups compared to hypertensive controls, and mean glomerular filtration rate of the left clipped kidneys of dihydralazine treated rats was significantly higher than in MK 421 treated rats: controls (N = 6) 1.03 +/- 0.03, dihydralazine-group (N = 10) 0.28 +/- 0.07, MK 421-group (N = 9) 0.03 +/- 0.01 ml/min. Renal blood flows were comparable in both treated groups. Only the left kidneys of rats treated with MK 421 showed a prominent tubular atrophy. Seven days after declipping of the left renal artery and right nephrectomy a considerable restitution of the tubular structure had occurred in the MK 421-group. The recovery of tubular epithelial cells was paralleled by a rise in glomerular filtration rate: MK 421 group (N = 7) 1.25 +/- 0.08 ml/min. Thus, the clipped kidney in two kidney, one clip hypertensive rats showed functional and morphological signs of impairment when systemic arterial pressure was reduced to the normal range. The alterations of the clipped kidney were most pronounced in rats with renin-angiotensin system-blockade.     

Hydronephrosis causes salt-sensitive hypertension and impaired renal concentrating ability in mice

Aim: Hypertension is a common disease in the industrialized world and approximately 5% of all cases are secondary to kidney malfunction. We have recently shown that hydronephrosis due to partial unilateral ureteral obstruction (PUUO) causes salt‐sensitive hypertension in rats. The mechanisms are still unclear, but appear to be intrarenal and primarily located to the diseased kidney. In the present study, we have developed a model for PUUO to study if hydronephrotic mice develop salt‐sensitive hypertension. Methods: PUUO was created in 3‐week‐old mice (C57bl/6J). Blood pressure and heart rate were measured telemetrically in adult animals on normal and high salt diets. Metabolism cages were used to study the renal excretion of electrolytes and water. Plasma samples for renin analysis were collected and renal histological changes were evaluated. Results: All hydronephrotic animals developed salt‐sensitive hypertension that correlated to the degree of hydronephrosis. In hydronephrotic animals, blood pressure increased from 114 ± 1 mmHg on normal salt diet to 120 ± 2 mmHg on high salt diet, compared with 103 ± 1 to 104 ± 1 in controls. Hydronephrotic animals showed increased diuresis and reduced ability to regulate electrolyte concentration. No differences in plasma renin concentration were found between the groups. The parenchymal weight and glomerular area of contralateral kidneys were significantly increased in the hydronephrotic animals. Histopathology of the hydronephrotic kidneys displayed areas with fibrosis, inflammation and glomerular changes. Conclusion: This study provides a model for PUUO in mice and demonstrates the presence of salt‐sensitive hypertension and an impaired renal concentrating ability in mice which has not been described before.     

Reproduzierbarkeit einer Captopril-induzierten akuten Niereninsuffizienz durch Enalapril

Summary In this case we are reporting on a patient suffering from malignant renovascular hypertension and chronic renal failure due to occlusion of both renal arteries. The acute renal insufficiency after Captopril and later on after Enalapril treatment was fully reversible. We believe that the acute reversible renal insufficiency was caused by the blockage of glomerular autoregulation depending on Angiotensin II.

     

Glomerular structure in lithium-induced chronic renal failure in rats

The effects of long-term lithium administration on glomerular structure and intervention with angiotensin converting enzyme inhibitor (ACEI) were studied in rats. Male Wistar rats were fed a lithium-containing diet (Li) or control diet (C) for 16 weeks postnatally. Li-treated rats developed renal failure, hypertension and proteinuria. During the subsequent 24 weeks, subgroups were treated with ACEI. The kidneys were fixed by perfusion, and tissue blocks were serially cut for estimation of glomerular volume and glomerular characteristics by light microscopy. Mesangial and mesangial matrix volume fractions, surface density of capillary walls, basement membrane thickness and foot process width (FPW) were measured by electron microscopy. Glomerular volume was decreased in Li-rats, with increased intra-individual variation. In all Li-rats, some glomeruli (mean 27%) were abnormal, with severe changes in only three rats. Ultrastructural parameters obtained by systematic sampling of three glomeruli in each rat showed no differences among groups. Among Li-treated animals there was a significant correlation between FPW and albumin excretion per unit filtration surface, and between filtration surface per glomerulus and inulin clearance. In conclusion, long-term lithium administration to newborn rats caused marked changes in glomerular volume which were not associated with measurable changes in structural parameters. No effect of ACEI-treatment was detectable.     

Selective distribution of medial thickening in the renal vessels in experimental hypertension

Direct effects, especially the distribution of medial thickening due to chronic hypertension on the renal arterial tree, were examined pathologically and morphometrically in cats with one-kidney DOCA-salt hypertension. Twenty-one adult male cats were divided into three groups: (i) an experimental group of one-kidney DOCA-salt hypertension (12 cats): (ii) a uninephrectomized group without administration of DOCA and salt (four cats); and (iii) a group without uninephrectomy and administration of DOCA and salt (five cats). The duration of hypertension varied from 3 weeks to 4 months and the aortic blood pressure was monitored every 5 min. The increase of mean blood pressure (MBP) of the experimental group was 15–44 mmHg. A significant medial thickening of the right renal arterial tree was evaluated by a comparison of the right and left regression lines of each case between the midwall radius (R) and medial thickness (D) of arteries in a distended state. The evaluation was made separately for arteries with R values above or below 40 μm, because a regression line between R and D showed a maximum bend at a level of R from 30 to 40 μm. The arteries of the right kidney with a diameter less than 40 μm, corresponding to the interlobular arteries and afferent arterioles, showed significant medial thickening in six cases. Medial thickening was absent in other cats of the experimental group and cats of a control group given uninephrectomy alone. Increase of MBP during the hypertensive phase of these six cases was above 34.6 mmHG and all values of other cats without medial thickening were below this level. The renal arteries of the right kidney with a diameter larger than 40 μm showed medial thickening in only one cat. This preferential distribution of medial thickening of the interlobular arteries and afferent arterioles due to one kidney DOCA-salt hypertension was considered to be a direct effect of hypertension and a result of the specific functional (autoregulation of the renal blood flow) and structural features of these arteries.     

血浆型凝溶胶蛋白和纤连蛋白在糖尿病肾病肾组织的表达及其临床病理资料分析

目的 对血浆型凝溶胶蛋白(pGSN)和纤连蛋白(FN)在糖尿病肾病(DN)患者肾组织的表达及其临床病理学资料进行分析.方法 根据临床诊断,将肾活检诊断为DN的67例患者分为4组:DN或糖尿病(DM)组、DM或DN合并高血压组、DM或DN合并其他肾脏病组和单纯诊断为其他肾脏疾病组,而后者又可分为血糖正常和血糖升高两种.利用免疫组织化学方法检测pGSN和FN在上述组织的石蜡切片的表达情况,与临床资料结合进行统计学分析.结果 pGSN和FN主要表达在肾小球和肾小管中,尤其在纤维化的肾小球和肾小管表达最为明显,两者均与肾小球的硬化率(硬化肾小球/总肾小球数)相关,而与其他的临床指标没有明显相关性.在四组临床诊断分组中,临床DM症状不典型伴有肾脏改变且血糖升高组,其肾小球滤过率(eGFR)明显降低(P＜0.05).而血糖正常组,其凝血酶原时间(PT)、血糖、丙氨酸转氨酶(ALT)、二氧化碳结合力及糖化血红蛋白相较于其他组有统计学意义(P＜0.05).而DM或DN伴有高血压组的患者其凝血项检查中的凝血酶原时间活动度(PT％)、凝血酶原时间国际标准化比值(PTINR)、凝血酶时间(TT)的差异有统计学意义(P＜0.05),ATL、天冬氨酸氨基转移酶(AST)明显降低(P＜0.05).结论 pGSN和FN反映肾小球的纤维化程度.临床上不能明确诊断为DN的病人,肾活检确诊时其肾功能的损害更严重.伴有高血压的DN患者,其凝血系统及肝功发生明显变化.     

Selective planting of cationized,haptenized ovalbumin on the rat tubular basement membrane

We developed an experimental protocol for planting exogenous antigens with different molecular weights and charges on the constituents of the renal tubulointerstitium. The cationized antigens were injected selectively into the left renal arteries of Wistar rats. Antigen localization was documented by immunohistochemistry on frozen sections. Cationized bovine serum albumin (BSA; 68 kDa, isoelectric point =9.5) localized almost exclusively along the glomerular capillary wall. After application of highly cationic polyethyleneimine, cationized BSA given subsequently was found in a linear distribution along the glomerular capillary wall and along the peritubular capillaries. The fate of highly cationized ovalbumin conjugated with trinitrophenol (TNP-OA), subjected to gel filtration to obtain monomers (42 kDa, isoelectric point >10) differed; it was deposited in a linear pattern on the tubular basement membrane (TBM) and Bowman's capsule, and remained up to 36 h after injection. Noncationized, monomeric TNP-OA (42 kDa, isolectnic point =4.6) showed fine granular deposition in the tubular epithelium exclusively. These findings indicate that the barrier of the glomerular BM acts selectively on antigens with different molecular weights. They either settle on the peritubular capillaries, after passing the glomerular, or reach the urinary space, after which they are reabsorbed by the tubular epithelial cells to reach the TBM.     

慢性肾性高血压大鼠脑组织磁共振成像观察和超微结构的研究

目的研究慢性肾性高血压大鼠脑核磁共振成像(MRI)的变化和相应部位超微结构的改变。方法将SD大鼠分为对照组和模型组。用双肾双夹法建立肾性高血压动物模型，术后饲养12个月，用磁共振成像结合电镜观察大鼠脑组织的变化。结果1．正常组大鼠的血压、MRI表现及超微结构未发现异常。2．慢性肾性高血压模型大鼠血压升高；侧脑室旁尾壳核区域T22WI像上可见明显的条状高信号；髓鞘结构松散，可见轴突与髓鞘间及髓鞘板层间形成宽大的裂隙，部分神经纤维缺失，髓鞘脱落。结论慢性肾性高血压大鼠脑内出现明显的条状高信号，提示脑部神经纤维的病变可能己比较严重。     

Fibrinogen-like protein 2 expression correlates with microthrombosis in rats with type 2 diabetic nephropathy

Fibrinogen-like protein 2 (fgl2),a novel prothrombinase,is involved in microthrombosis.We examined fgl2 expression in the glomerular and tubulointerstitial capillaries and its correlation with microthromsis in rats with streptozocin-induced type 2 diabetic nephropathy.Our RT-PCR and immunoblotting analysis showed that fgl2 mRNA and protein levels were increased in microvascular endothelial cells of the glomeruli and renal interstitia at week 19 and became significantly elevated with the development of diabetic nephropathy (P < 0.01).Fgl2 was not or only weakly expressed in the renal tissues of normal rats.Furthermore,a direct significant correlation (r=0.543,P < 0.01) was found between fgl2 expression and microthrombotic capillaries in the renal tissues.Enzyme linked immunosorbent assays (ELISA) additionally showed that circulating TNF-α levels in rats with type 2 diabetes were significantly elevated and closely correlated with fgl2 expression (r=0.871,P < 0.01).Our results suggest that fgl2 may activate renal microthrombosis,thus contributing to glomerular hypertension and renal ischemia.     

Effects of maternal undernutrition on renal angiotensin II and chymase in hypertensive offspring

Intrauterine growth restriction (IUGR) can program the future development of hypertension in adulthood. The renin-angiotensin system has been reported to play a role in IUGR-induced hypertension. The aims of this study were to investigate the effects of IUGR on renal angiotensin-converting enzyme (ACE), angiotensin II (Ang II) and chymase in IUGR-induced hypertension. Timed pregnant Sprague-Dawley rats received 50% rations of control food intakes from days 15 to 21 of gestation. Control rats received regular food throughout the pregnancies. Arterial blood pressure and glomerular number were measured and immunohistochemical studies were performed on kidney tissues in adult male offspring at 16 weeks of age. IUGR rats exhibited significantly lower body and kidney weights and reduced number of glomeruli when compared with control rats. IUGR rats had significantly higher systolic blood pressure than control rats. Immunoreactivity of ACE was comparable between control and IUGR rats whereas immunoreactivities of chymase and Ang II were significantly higher in IUGR rats than in control rats. In conclusion, immunohistochemical studies document up-regulation of ACE-independent Ang II and chymase in IUGR kidney and indicate that overactivity of chymase may result in increased intrarenal Ang II production, which could contribute to the development of hypertension in intrauterine undernourished rats.