Renal histological alterations induced by acute exposure of titanium dioxide nanoparticles / Alteraciones histológicas renales inducidas por la exposición aguda de nanopartículas de dióxido de titanio

SUMMARY: Titanium dioxide nanoparticles (TiO2 NPs) are widely used in many commercial products, nanomedicine, agriculture, personal care products, different industries and pharmaceutical preparations with potential risk in human health and the environment. The current work was conducted to investigate the renal damage that might be induced by the acute toxicity TiO2 NPs. A total of 40 healthy male adult Wistar albino rats (Rattus norvegicus) were exposed to TiO2 NPs (126, 252, 378 mg/kg bw) for 24 and 48 h. Fresh portions of the kidneys from each rat were processed for histological and histochemical alterations. In comparison with respective control rats, exposure to TiO2 NPs has marked the following glomerular, tubular and interstitial alterations including the followings: glomerular congestion, Bowman's capsule swelling and dilatation, inflamed glomeruli, renal tubules cloudy swelling, karyorrhexis, karyolysis, infiltration of inflammatory cells, congestion, necrosis, hydropic degeneration, dilatation and congestion of blood vessels, hyaline droplets and hyaline casts precipitation, interstitial edema and fibrosis. From the findings of the current work one may conclude that TiO2 NPs are capable of inducing kidney damage with more insulation in the cortex and the proximal convoluted tubules than the medulla and the distal ones respectively. In addition, it might be concluded that renal damage induced by these nanomaterials is dose and duration of exposure dependent. Further hematological, biochemical, immunohistochemical, and ultra-structural studies are recommended.

RESUMEN: Las nanopartículas de dióxido de titanio (TiO2 NP) se usan ampliamente en muchos productos comerciales, nanomedicina, agricultura, productos para el cuidado personal, diferentes industrias y preparaciones farmacéuticas con riesgo potencial para la salud humana y el medio ambiente. El trabajo actual se realizó para investigar el daño renal que podría ser inducido por la toxicidad aguda NP de TiO2. Un total de 40 ratas Wistar albinas adultas sanas (Rattus norvegicus) fueron expuestas a TiO2 NP (126, 252, 378 mg / kg de peso corporal) durante 24 y 48 h. Las muestras de los riñones de las ratas se procesaron para estudios histológicos e histoquímicos. En comparación con las ratas control, la exposición de las ratas a TiO2 NP presentaron las siguientes alteraciones glomerulares, tubulares e intersticiales: congestión glomerular, dilatación de la cápsula de Bowman, inflamación glomerular, túbulos renales aumentados, cariorrexis, cariólisis, infiltración de células inflamatorias, congestión, necrosis, degeneración hidrópica, dilatación y congestión de vasos sanguíneos, gotas y precipitaciones hialina, edema intersticial y fibrosis. A partir de los hallazgos del trabajo actual, se puede concluir que las NP de TiO 2 son capaces de inducir daño renal con más aislamiento en la corteza y en los túbulos contorneados proximales que en la médula y los túbulos contorneados distales, respectivamente. Además, se podría concluir que el daño renal inducido por estos nanomateriales depende de la dosis y la duración de la exposición. Se recomiendan estudios adicionales hematológicos, bioquímicos, inmunohistoquímicos y ultraestructurales.

Protective effect of resveratrol against morphine damage to kidneys of mice / Efecto protector de resveratrol contra el daño de la morfina en riñones de ratones

SUMMARY: Morphine produces free radicals and cause apoptosis in some cell. Resveratrol (RSV) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury. 48 male mice were randomly assigned to 8 groups. In this study, various doses of RSV (2, 8 and 20 mg/kg) and RSV plus Morphine (2, 8 and 20 mg/kg) were administered intraperitoneally to male mice for 20 consequent days and weight of kidneys, biochemical characteristics, morphometric markers and blood serum nitric oxide level were studied. The results indicated that morphine administration significantly increased the mean diameter of glomerulus and distal and proximal convoluted tubule, Lactate dehydrogenase (LDH), Blood urea nitrogen (BUN), creatinine and nitric oxide levels compared to the saline group (P<0.05). However, RSV and RSV plus morphine in all doses significantly decreased glomeruli number and LDH, BUN, creatinine and nitric oxide levels compared to morphine groups (p<0.05). Thus, it seems that resveratrol improved kidney damages induced by morphine in mice.

RESUMEN: La morfina produce radicales libres y causa apoptosis en algunas células. El resveratrol (RSV) es un tipo de fenol natural y una fitoalexina producida por varias plantas en respuesta a una lesión. Se asignaron al azar 48 ratones machos a 8 grupos. En este estudio se administraron varias dosis de RSV (2, 8 y 20 mg/kg) y RSV más morfina (2, 8 y 20 mg/kg) intraperitoneal en ratones machos durante 20 días consecutivos y se estudió el peso de los riñones, las características bioquímicas, los marcadores morfométricos y el nivel de óxido nítrico en suero sanguíneo. Los resultados indicaron que la administración de morfina aumentó significativamente el diámetro medio del glomérulo y de los túbulos distal y proximal, los niveles de lactato deshidrogenasa (LDH), nitrógeno ureico en sangre (BUN), la creatinina y el óxido nítrico en comparación con el grupo salino (p <0,05). Sin embargo, el RSV y el RSV más morfina en todas las dosis redujeron significativamente el número de glomérulos y LDH, BUN, la creatinina y el óxido nítrico en comparación con los grupos de morfina (p <0,05). Por lo tanto, los resultados podrían indicar que el resveratrol mejoró el daño renal inducido por la morfina en ratones.

Hydrochloride pioglitazone protects diabetic rats against podocyte injury through preserving glomerular podocalyxin expression / O cloridrato de pioglitazona protege ratos diabéticos contra a injúria aos podócitos por meio da preservação da expressão de podocalixina glomerular

Objective: We sought to test the effect of different dosages of pioglitazone (PIO) on the glomerular expression of podocalyxin and urinary sediment podocalyxin excretion and to explore the potential renoprotective mechanism. Materials and methods: Type 1 diabetes induced with streptozotocin (65 mg/kg) in 36 male Sprague-Dawley rats were randomly allocated to be treated with vehicle or 10, 20, 30 mg/kg/d PIO respectively for 8 weeks. Eight rats were enrolled in the normal control group. Results: At 8th week, rats were sacrificed for the observation of kidney injury through electron microscope. Glomerular podocalyxin production including mRNA and protein were determined by RT-PCR and immunohistochemistry respectively. Levels of urinary albumin excretion and urinary sediment podocalyxin, kidney injury index were all significantly increased, whereas expression of glomerular podocalyxin protein and mRNA were decreased significantly in diabetic rats compared to normal control. Dosages-dependent analysis revealed that protective effect of PIO ameliorated the physiopathological changes and reached a peak at dosage of 20 mg/kg/d. Conclusion: PIO could alleviate diabetic kidney injury in a dose-dependent pattern and the role may be associated with restraining urinary sediment podocalyxin excretion and preserving the glomerular podocalyxin expression. .

Objetivo: Buscamos testar os efeitos de diferentes doses de pioglitazona (PIO) sobre a expressão glomerular de podocalixina e sobre a excreção de podocalixina em células do sedimento urinário, além de explorar o potencial mecanismo de proteção renal. Materiais e métodos: O diabetes tipo 1 foi induzido em 36 ratos Sprague-Dawley machos com estreptozotocina (65 mg/kg). Os animais foram tratados apenas com o veículo, ou com 10, 20, 30 mg/kg/d de PIO por 8 semanas. Oito ratos foram colocados no grupo controle. Resultados: Na oitava semana, os ratos foram sacrificados para se observar a lesão renal em microscopia eletrônica. A produção de podocalixina glomerular, incluindo mRNA e proteína, foi determinada por RT-PCR e imuno-histoquímica, respectivamente. Os níveis urinários de albumina e podocalixina nas células do sedimento urinário e o índice de lesão renal estavam todos significativamente aumentados, enquanto a expressão glomerular da proteína podocalixina e do mRNA estava significativamente diminuída em ratos diabéticos comparados com o controle normal. A análise dos efeitos dose-dependentes revelou que o efeito protetor da PIO melhorou as mudanças fisiopatológicas e atingiu um pico na dose de 20 mg/kg/dia. Conclusão: A PIO pode melhorar a injúria renal de forma dose-dependente e este papel pode estar associado com a prevenção da excreção de podocalixina nas células do sedimento urinário e com a preservação da expressão glomerular de podocalixina. .

Renal corpuscles were protected from dichlorvos: induced morphological alterations in rats by antioxidant vitamins / Protección de corpúsculos renales ante alteraciones morfológicas inducidas por el diclorvos en ratas mediante el uso de vitaminas antioxidantes

Dichlorvos (DDVP), an organophosphorus pesticide is a volatile compound which enters the human body through oral, dermal and inhalational routes and is excreted via the kidney. This study assessed the effects of DDVP on the histology of the kidney. Twenty five male rats (75.05 ± 5.55 g) were divided into 5 groups of 5 rats per group as follows: Unexposed group, exposure to DDVP alone for 5 weeks, and 3 other groups exposed to DDVP for 5 weeks in addition to supplement with Vitamin E, vitamin C, and red palm oil (RPO). Rats were exposed to DDVP in poorly ventilated cardboard cages for 4 hours daily. On completion of exposure, rats were euthanized and tissue processed by routine paraffin wax method and stained with H&E. Morphological alterations monitored by histological and morphometric studies using the graticule and software packages. Data were analyzed with ANOVA and p<0.05 considered as significant. DDVP caused significant reduction (10%) in the maximum glomerular diameter and 18% reduction in the maximum width of the renal corpuscle when compared with unexposed rats. However, VTE, VTC, and RPO significantly elevated the maximum glomerular diameter by 21%, 22%, 23% the respectively. Similarly, VTE, VTC, and RPO significantly elevated the maximum width of the renal corpuscle by 17%, 19%, 20% respectfully. Glomerular tuft cellularity was neither affected by DDVP treatment nor by vitamin augmentation. Inhaled DDVP caused histological alterations in the microscopic anatomy of renal corpuscles of rat which was mitigated by vitamin supplementation. Data suggest involvement of prolonged DDVP use in the aetiology of renal failure.

El diclorvos (DDVP), un pesticidas organofosforado, es un compuesto volátil que entra en el cuerpo humano a través de la vía oral, dérmica y por rutas inhalación, excretándose por vía renal. Este estudio evaluó los efectos histológicos del DDVP sobre el riñón. Veinticinco ratas machos (75,05±5,55 g) se dividieron en 5 grupos de 5 ratas cada uno: grupo no expuesto, expuesto a DDVP durante 5 semanas, y otros 3 grupos expuestos a DDVP durante 5 semanas, suplementados con vitamina E (VTE), vitamina C (VTC) y aceite de palma roja (APR). Las ratas fueron expuestas a DDVP en jaulas de cartón con poca ventilación por 4 horas diarias. Al término de la exposición, las ratas se sacrificaron y el tejido fue procesado para inclusión en parafina y tinción con H&E. Las alteraciones morfológicas se evaluaron mediante estudios histológicos y morfométricos utilizando retículas y software. Los datos se analizaron con la prueba ANOVA considerado un p<0,05 como significativo. El DDVP causó una reducción significativa (10%) en el diámetro máximo glomerular y ancho máximo del copúsculo renal (18%), en comparación con las ratas no expuestas. Sin embargo, el diámetro máximo glomerular fue significativamente elevado con VTE, VTC y APR en 21%, 22% y 23%, respectivamente, así como para el ancho máximo del corpúsculo renal por 17%, 19% y 20%, respectivamente. La celularidad de la red glomerular no fue afectada por el DDVP ni aumentó con el tratamiento de vitamina. El DDVP inhalado provocó alteraciones histológicas en la anatomía microscópica de los corpúsculos renales de rata, las que fueron mitigadas por la suplementación de vitamina. Los datos sugieren relación entre la exposición prolongada a DDVP y la etiología de la insuficiencia renal.

Histologic alterations of rat kidneys perfused with a Euro-Collins diltiazem solution / Alterações histológicas ocorridas em rins de ratos perfundidos com solução de Euro-Collins associada à diltiazem

PURPOSE: Analyse the histologic changes of rat kidneys perfused with isotonic saline solution (ISS), Euro-Collins solution (ECS) and Euro-Collins solution with diltiazem (ECSD). METHODS: Thirty-six Wistar rats were used divided equally, as follow: group A (ISS), group B (ECS) and group C (ECSD). Through a catheter placed into the abdominal aorta, a renal perfusion was performed using a solution according to the group to which the animal belonged. After the complete perfusion, bilateral nephrectomy was performed and the organs were preserved under hypothermia for five distinct periods of time. Glomerulus and tubule were evaluated through optical microscopy. RESULTS: Renal perfusion with ECS and ECSD proved effectiveness in the preservation of the organs up to 36 hours and an increase in the percentage of injured glomeruli was noticed only in the period of 48 hours. CONCLUSIONS: The results showed that exists an association between the tubular injury and the glomeruli lesion degree; kidneys with a higher degree of tubular damage were related to severe glomerular lesion. Also, the addition of a calcium channel blocker, diltiazem, to the ECS for the renal perfusion does not decrease the percentage of glomerular lesion.

OBJETIVO: Analisar as alterações histológicas nos rins de ratos perfundidos com solução salina isotônica (ISS), solução Euro-Collins (ECS) e solução Euro-Collins com diltiazem (ECSD). MÉTODOS: Foram divididos, de forma igual, 36 ratos Wistar, como se segue: grupo A (ISS), grupo B (ECS), grupo C (ECSD). Através de um cateter localizado na aorta abdominal, foi realizada a perfusão renal com a solução de acordo com o grupo ao qual o animal pertencia. Após a perfusão total, realizou-se nefrectomia bilateral com a preservação dos órgãos sob hipotermia por cinco períodos distintos de tempo. Glomérulos e túbulos foram avaliados por microscopia óptica. RESULTADOS: Tanto a perfusão renal com ECS quanto a com ECSD provaram sua efetividade na preservação dos órgãos em até 36 horas e aumento da porcentagem de glomérulos injuriados foi notada apenas no período de 48 horas. CONCLUSÕES: Os resultados mostraram haver uma correlação entre a injúria tubular e o grau de lesão glomerular; rins com um maior grau de dano tubular foram relacionados com lesão glomerular severa. Além disso, a adição de um bloqueador de canal de cálcio, diltiazem, à ECS para a perfusão renal não diminui a porcentagem de lesão glomerular.

BTCI enhances guanylin-induced natriuresis and promotes renal glomerular and tubular effects

Guanylin and uroguanylin are small cysteine-rich peptides involved in the regulation of fluid and electrolyte homeostasis through binding and activation of guanylyl cyclases signaling molecules expressed in intestine and kidney. Guanylin is less potent than uroguanylin as a natriuretic agent and is degraded in vitro by chymotrypsin due to unique structural features in the bioactive moiety of the peptide. Thus, the aim of this study was to verify whether or not guanylin is degraded by chymotrypsin-like proteases present in the kidney brush-border membranes. The isolated perfused rat kidney assay was used in this regard. Guanylin (0.2 µM) induced no changes in kidney function. However, when pretreated by the black-eyed pea trypsin and chymotrypsin inhibitor (BTCI - 1.0 µM; guanylin - 0.2 µM) it promoted increases in urine flow (deltaUF of 0.25 ± 0.09 mL.g-1/min, P < 0.05) and Na+ excretion ( percent delta ENa+ of 18.20 ± 2.17, P < 0.05). BTCI (1.0 µM) also increased percentENa+ (from 22.8 ± 1.30 to 34.4 ± 3.48, P < 0.05, 90 minutes). Furthermore, BTCI (3.0 µM) induced increases in glomerular filtration rate (GFR; from 0.96 ± 0.02 to 1.28 0.02 mL.g-1/min, P < 0.05, 60 minutes). The present paper strongly suggests that chymotrypsin-like proteases play a role in renal metabolism of guanylin and describes for the first time renal effects induced by a member of the Bowman-Birk family of protease inhibitors.

Guanilina e uroguanilina são peptídeos pequenos, ricos em cisteína, envolvidos na regulação da homeostase de fluidos e eletrólitos através da ligação e ativação da guanilato ciclase expressa no intestino e nos rins. A guanilina é menos potente do que a uroguanilina como agente natriurético e é degradada in vitro pela quimiotripsina devido a características estruturais únicas no domínio bioativo do peptídeo. Portanto o objetivo deste trabalho foi verificar se a guanilina é degradada por proteases tipo quimiotripsina, presentes na membrana da borda em escova dos rins. Para esta investigação, foi usado o modelo do rim isolado de rato perfundido. A Guanilina (0,2 µM) não induziu mudanças na função renal. Entretanto, quando pré-tratada com inibidor de tripsina e de quimiotripsina de black-eyed pea (BTCI - 1,0 µM; guanilina - 0,2 µM) promoveu um aumento no fluxo urinário (deltaUF de 0,25 ± 0,09 mL.g-1/min, P < 0,05) e na excreção de Na+ ( por centoDENa+ de 18,20 ± 2,17, P < 0,05). BTCI (1,0 µM) também aumenta por centoENa+ (de 22,8 ± 1,30 a 34,4 ± 3,48, P < 0,0590 minutos). Além disto, BTCI (3,0 µM) induziu um aumento da taxa de filtração glomerular (GFR; de 0,96 ± 0,02 para 1,28 ± 0,02 mL.g-1/min, P < 0,05, 60 minutos). O presente trabalho sugere fortemente que proteases semelhantes à quimiotripsina desempenham um papel no metabolismo renal de guanilinas e descreve, pela primeira vez, os efeitos renais induzidos por um membro da família de inibidores de proteases do tipo Bowman-Birk.

Effect of D-alpha-tocopherol on tubular nephron acidification by rats with induced diabetes mellitus

The objective of the present study was to determine if treatment of diabetic rats with D-alpha-tocopherol could prevent the changes in glomerular and tubular function commonly observed in this disease. Sixty male Wistar rats divided into four groups were studied: control (C), control treated with D-alpha-tocopherol (C + T), diabetic (D), and diabetic treated with D-alpha-tocopherol (D + T). Treatment with D-alpha-tocopherol (40 mg/kg every other day, ip) was started three days after diabetes induction with streptozotocin (60 mg/kg, ip). Renal function studies and microperfusion measurements were performed 30 days after diabetes induction and the kidneys were removed for morphometric analyses. Data are reported as means ± SEM. Glomerular filtration rate increased in D rats but decreased in D + T rats (C: 6.43 ± 0.21; D: 7.74 ± 0.45; D + T: 3.86 ± 0.18 ml min-1 kg-1). Alterations of tubular acidification observed in bicarbonate absorption flux (JHCO3) and in acidification half-time (t/2) in group D were reversed in group D + T (JHCO3, C: 2.30 ± 0.10; D: 3.28 ± 0.22; D + T: 1.87 ± 0.08 nmol cm-2 s-1; t/2, C: 4.75 ± 0.20; D: 3.52 ± 0.15; D + T: 5.92 ± 0.19 s). Glomerular area was significantly increased in D, while D + T rats exhibited values similar to C, suggesting that the vitamin prevented the hypertrophic effect of hyperglycemia (C: 8334.21 ± 112.05; D: 10,217.55 ± 100.66; D + T: 8478.21 ± 119.81æm²). These results suggest that D-alpha-tocopherol is able to protect rats, at least in part, from the harmful effects of diabetes on renal function.

Impact of Cyclosporin on Podocyte ZO-1 Expression in Puromycin Aminonucleoside Nephrosis Rats

Puromycin aminonucleoside (PAN) -induced nephrosis is a well-described model of human idiopathic nephrotic syndrome, but the mechanism of PAN's effect is not completely understood. To investigate whether proteinuria in the PAN model is associated with an alteration of zonula occludens-1 (ZO-1) expression within the glomeruli, and whether cyclosporin A (CsA) has an effect on proteinuria and ZO-1 expression in this model, eighteen Sprague Dawley (SD) rats were assigned into three groups. Twelve rats received a single intraperitoneal injection of PAN (15 mg/100 g). The other six rats received an equal volume of saline (normal control group; control). CsA solution was administered intraperitoneally once a day for 20 days after the PAN injection (n=6, PAN+CsA). The remaining six rats received PAN, but they didn't receive CsA (n=6, PAN). Compared to control rats (35.1 +/- 5.4 mg/day), the 24-hour urinary protein excretion on day 18 was significantly higher in the PAN rats (1021.9 +/- 128.9 mg/day, p< 0.01), and the CsA treatment partly reversed the increase in proteinuria in the PAN rats (556.4 +/- 102.3 mg/day, p< 0.05). Glomerular ZO-1 protein expressions were significantly increased in the PAN rats as compared to the control group on day 20 (176%, p< 0.01). CsA treatment for 20 days in the PAN rats inhibited the increase in ZO-1 protein expression by 71.1% (p< 0.05). CsA treatment significantly diminished the glomerular ZO-1 expression in the PAN rats as assessed by immunohistochemistry. CsA treatment significantly reduced proteinuria and the diminished glomerular ZO-1 expression in a PAN nephrosis rat model. These findings suggest the potential role of the slit diaphragm associated proteins in the development of the nephrotic syndrome, and CsA decreased the proteinuria probably by a direct action on the expression of these proteins in podocytes. Further investigations are needed to clarify the role of slit diaphragm associated proteins in the development of PAN nephrosis.

Inducible Nitric Oxide Synthase (iNOS) Expression Is Increased in Lipopolysaccharide (LPS)-Stimulated Diabetic Rat Glomeruli: Effect of ACE Inhibitor and Angiotensin II Receptor Blocker

Previously, we reported that high glucose enhanced cytokine-induced nitric oxide (NO) production by rat mesangial cells (MCs), and that the enhanced expression of the iNOS pathway may promote extracellular matrix accumulation by MCs. The present study was designed to examine whether the iNOS pathway is pathologically altered in experimental diabetic nephropathy, and whether therapy with angiotensin converting enzyme (ACE) inhibitor (imidapril: I) or angiotensin II type I receptor (AT1) blocker (L-158,809: L), ameliorates these changes. Male Sprague-Dawley rats were injected with diluent (control: C) or streptozotocin. At sacrifice after 4, 8 and 12 weeks, rats underwent either a 4 hour placebo or an intraperitoneal lipopolysaccharide (LPS, 2 mg/kg) challenge. Systolic blood pressure (SBP) and urinary protein excretion (UPE) increased significantly in diabetic (D) rats compared with C. The basal expression of glomerular iNOS mRNA was increased in D rats compared with that of C rats, by reverse- transcription (RT)-polymerase chain reaction (PCR), whereas there was no significant difference in the level of protein by Western blot analysis. Upon LPS stimulation, the iNOS mRNA and protein expression was significantly elevated in D rats. In D rats, this up-regulation, of LPS-stimulated iNOS expression, was equally ameliorated both by I and L in mRNA and protein levels. From immunohistochemistry (IHC), there was a negative staining for the iNOS within the glomeruli of five C rats without LPS treatment, but one of four rats, with LPS treatment, showed minimal iNOS staining in the glomeruli. In D rats, the glomerular mesangium and podocytes were positive for iNOS in each of three out of five rats with, and without, LPS treatment. In conclusion, LPS-stimulated glomerular iNOS expression was enhanced in diabetic pnephropathy, and the activation of angiotensin II may play a role in this enhancement.

Changes of glomerular basement membrane components in Vacor-induced diabetic nephropathy

OBJECTIVES: The thickening of the glomerular basement membrane in rats after Vacor ingestion was examined by electron microscopy. This study was performed to elucidate which biochemical components changed in the glomerular basement membrane after Vacor-induced diabetic glomerulopathy. METHODS: Immunohistochemical analyses of type IV collagen, laminin, fibronectin and chondroitin sulfate proteoglycan were performed. A single dose of Vacor (molecular weight 272), 80 mg/kg, was administered to adult male Wistar rats by orogastric canule, and the animals were sacrificed at 0.5, 1, 3, 7, 14, 28 and 56 days after administration. RESULTS: Mild thickening of the glomerular basement membrane was evident 7 days after Vacor administration, and the width of the glomerular basement membrane was more than twice that of normal controls at 28 and 56 days. Significantly increased expressions of type IV collagen, laminin, fibronectin and neutral polysaccharide in the thickened glomerular basement membrane were noted 14 to 56 days after administration, and a mildly increased expression of chondroitin sulfate proteoglycan appeared between 3 to 7 days. CONCLUSION: These abnormally increased glomerular basement membrane components might be part of what causes diabetic nephropathy after Vacor administration.

Glomerular hemodynamics during abortion induced by RU 486 and sepsis in rats

1. Acute renal failure is a very common consequence of septic abortion. Whole kidney and glomerular hemodynamics were evaluated in virgin (V), pregnant (PREG) and aborted (ABOR) euvolemic Munich-Wistar rats before and after E. coli (0111-B4) endotoxin (LPS) infusion in order to evaluate the effect of septic abortion on the renal microcirculation. 2. Abortion induced by RU 486 blunted the increase in glomerular filtration rate (GFR) induced by normal pregnancy (0.86 +/- 0.03 vs 0.63 +/- 0.07 ml/min, P < 0.05). In virgin rats, RU 486 did not modify the parameters of renal function. Significant alterations occurred in whole kidney and single nephron function. However, the changes in whole kidney function in the ABOR group were significantly higher than those observed for the V group (reductions in GFR were 42 in V and 80 in ABOR, RPF decreased 34 in V and 76 in ABOR, TRVR increased 82 in V and 400 in ABOR). 3. Mean single nephron glomerular filtration rate (SNGFR) was reduced in all groups after LPS (44 in V, 43 in V+RU, 55 in PREG, 60 in ABOR), due to significant decreases in glomerular plasma flow rate, QA (42 in V, 55 in V+RU, 53 in PREG, 57 in ABOR) and in glomerular ultrafiltration coefficient, Kf (46 in V, 47 in V+RU, 45 in PREG, 67 in ABOR). 4. These data show that LPS induced significant alterations in renal function in all groups. However, aborted rats were more sensitive to the effects of LPS than V rats. These results indicate that abortion may potentiate the effects of endotoxemia on renal function elevating the extent of acute renal failure and thus the mortality rate.