A study on the toxic effect of different doses of diclofenac sodium on the development of the kidney in the postnatal period / Estudio sobre el efecto tóxico de diferentes dosis de diclofenaco sódico en el desarrollo del riñón en el período postnatal

The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9 mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring's from 0-7 days after birth were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels, increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group. Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects that are dose-dependent in the prenatal subjected kidney to this drug.

Se investigaron los efectos tóxicos de diferentes dosis de diclofenaco sódico (DS) en el riñón de ratas, durante su período postnatal (0-7 días), por métodos morfométricos e inmunohistoquímicos. Para este propósito, se utilizaron 20 crías macho, de ratas Wistar albinas, y se dividieron en 5 grupos principales. El grupo Ia sirvió como control normal, el grupo fisiológico Ib recibió solución salina normal, el grupo II recibió una dosis baja de DS (3,9 mg/kg), el grupo III recibió una dosis media de DS (9 mg/kg) y el grupo IV recibió una dosis alta de DS (18 mg/kg). Se administraron los medicamentos de 0 a 7 días después del nacimiento de las ratas. En el octavo día de vida postnatal, todos los animales fueron sacrificados. Luego, se analizaron las muestras de riñón. Mediante hematoxilina-eosina se evidenció degeneración y necrosis, aparente atrofia de los glomérulos, infiltración de células mononucleares, vasos congestionados, aumento del tejido fibroso y distorsión de los túbulos contorneados proximales, con interrupción del margen en cepillo del grupo tratado con DS. Se detectó un aumento del nivel de caspasa-3 y regulación al alza de TNF-α con diferentes dosis de DS. A la luz de nuestros hallazgos, la DS puede provocar efectos adversos en el riñón, que dependen de la dosis de este medicamento administrada en el período posnatal.

Impact of gender in early structural changes of contrast induced nephropathy in rats / Impacto do gênero em alterações estruturais precoces da nefropatia induzida por contraste em ratos

Abstract Introduction: Contrast-induced nephropathy (CIN) is a major iatrogenic cause of acute kidney injury. Experimental studies have shown that intravascular injection causes intense vacuolization of the contrast agent in the proximal renal tubules cells, preceding the increase in serum creatinine, and that the female may be at a higher risk for CIN. Objective: To study the early kidney histomorphometric changes in contrast-induced nephropathy according to the gender. Methods: Twenty previously uninephrectomized Wistar rats were divided into 4 groups (n = 5): control males; control females; contrast exposed males; and contrast exposed females. The animals were sacrificed immediately after contrast administration and kidney tissue samples were collected for histomorphometric analysis. The research project was approved by the Research Ethics Committee of the School of Medicine of Universidade Federal Fluminense. Results: There was a more intense presence of microvacuoles in proximal tubules in the rats exposed to contrast than in the control groups. Such proximal tubular vacuolation was more intensive in the female rats (p = 0.001). Conclusion: Proximal tubular vacuolation is a very early change in CIN and is more intensive in female than in male rats.

Resumo Introdução: A nefropatia induzida por contraste (NIC) é uma das principais causas iatrogênicas de lesão renal aguda. Estudos experimentais têm demonstrado que a injeção intravascular do agente de contraste provoca vacuolização intensa nas células dos túbulos renais proximais, que precede o aumento da creatinina sérica, e que a fêmea podem estar em maior risco de CIN. Objetivo: Estudar as primeiras mudanças histomorfométricas renais na nefropatia induzida por contraste de acordo com o gênero. Métodos: Vinte ratos Wistar anteriormente uninefrectomizados foram divididos em 4 grupos (n = 5): machos de controle; fêmeas de controle; machos expostos ao contraste e fêmeas expostas ao contraste. Os animais foram sacrificados imediatamente após a administração de contraste e amostras de tecido de rim foram coletadas para análise histomorfométrica. O projeto de pesquisa foi aprovado pelo Comitê de Ética em Pesquisa da Faculdade de Medicina da Universidade Federal Fluminense. Resultados: Houve presença mais intensa de microvacuolização em túbulos proximais nos ratos expostos ao contraste do que nos grupos de controle. Tal vacuolização tubular proximal foi mais intensa nos ratos do sexo feminino p = 0,001). Conclusão: Vacuolização do tpubulo proximal é uma mudança precoce na CIN e é mais intensa em ratos fêmeas do que em ratos machos.

Angiotensin III increases monocyte chemoattractant protein-1 expression in cultured human proximal tubular epithelial cells

BACKGROUND/AIMS: We investigated whether angiotensin III (Ang III) is involved in monocyte recruitment through regulation of the chemokine monocyte chemoattractant protein-1 (MCP-1) in cultured human proximal tubular epithelial cells (HK-2 cells). METHODS: We measured MCP-1 levels in HK-2 cells that had been treated with various concentrations of Ang III and Ang II type-1 (AT1) receptor antagonists at various time points. The phosphorylation states of p38, c-Jun N-terminal kinases (JNK), and extracellular-signal-regulated kinases were measured in Ang III-treated cells to explore the mitogen-activated protein kinase (MAPK) pathway. MCP-1 levels in HK-2 cell-conditioned media were measured after pre-treatment with the transcription factor inhibitors curcumin or pyrrolidine dithiocarbamate. RESULTS: Ang III increased MCP-1 protein production in dose- and time-dependent manners in HK-2 cells, which was inhibited by the AT1 receptor blocker losartan. p38 MAPK activity increased significantly in HK-2 cells exposed to Ang III for 30 minutes, and was sustained at higher levels after 60 minutes (p < 0.05). Total phosphorylated JNK protein levels tended to increase 20 minutes after stimulation with Ang III. Pre-treatment with a p38 inhibitor, a JNK inhibitor, or curcumin significantly inhibited Ang III-induced MCP-1 production. CONCLUSIONS: Ang III increases MCP-1 synthesis via stimulation of intracellular p38 and JNK MAPK signaling activity and subsequent activated protein-1 transcriptional activity in HK-2 cells.

Impairment of renal structure and function following heterogeneous chemical mixture exposure in rats.

Renal structural and functional alterations following an exposure to a heterogeneous chemical mixture (HCM) of phthalic acid di butyl ester, 1, 2–dichlorobenzene, cadmium chloride and chromium trioxide, administered through oral gavage in low doses (1/100 and 1/1000 of LD50 value of individual chemical) for 60 days, followed by withdrawal till 120 days resulted in significant rise in kidney lipid peroxidation and fall in the activities of enzymatic antioxidants. However, withdrawal of HCM treatment restored most of these altered parameters. Degenerative changes in the kidney included proximal convoluted tubules devoid of brush boarder with cytoplasmic blebbing, dissolution and sloughing of nuclei. Cortical glomeruli were also affected with epithelial disintegration, pyknosis of podocyte nuclei and mesengial cell hyperplasia. The morphological alterations recovered fully in the low dose compared to the high dose treatment group.

Tranilast attenuates TGF-beta1-induced epithelial-mesenchymal transition in the NRK-52E cells

We previously reported that tranilast can halt the pathogenesis of chronic cyclosporine nephrotoxicity in rats via the transforming growth factor-beta [TGF-beta] /Smad pathway, an important signaling system involved in epithelialmesenchymal transition [EMT], but the exact underlying cellular mechanisms are not yet clear. Thus, by selecting [0]TGF-beta1-induced normal rat kidney proximal tubular epithelial cells [NRK-52E] as a model, we demonstrated potential modifying effect of tranilast on EMT-induced by TGF-beta1 in vitro. NRK-52E cells were incubated with the blank vehicle [Dulbecco's modified Eagle's medium and F-12 [DMEM/F12] added with 10% fetal bovine serum [FBS]], 10 ng/ml TGF-beta1 alone or together with 100, 200 or 400microM tranilast for 48 h after incubation in medium containing 1% FBS for 24 h. Cell morphological changes were observed to confirm occurrence of EMT. Protein expressions of two typical markers of EMT, E-cadherin and alpha-smooth muscle actin [alpha-SMA], were assessed by western blotting and flow cytometry, respectively. Our results showed that TGF-beta1 induced spindle-like morphological transition, the loss of Ecadherin protein and upregulation of expression of alpha-SMA. However, the TGF-beta1-produced changes in cellular morphology, E-cadherin and alpha-SMA were inversed by tranlilast in concentration-dependent manner. Our findings indicate that tranilast can directly inhibit EMT. Thus, it may be implied that regulation of EMT be the target to prevent renal tubulointerstitial fibrosis.

Effects of diclofenac sodium on renal parenchyma and prevention by vitamin-E in adult albino rats

To determine the preventive role of Vitamin E on renal parenchyma after given of Diclofenac Sodium in albino rats. Experimental Study This study was conducted in the Department of Anatomy Baqai Medical University and Muhammad Medical College, Mirpurkhas from June 2011 to November 2011, For this experimental study, 30 albino rats were taken. They were divided into three groups ; A, B and C. The animals in group-A given normal saline 10 ml/kg per day. Group-B received diclofenac sodium 2 mg/kg per day and group-C receives diclofenac sodium 2mg/kg/day dissolved in distilled water with vitamin-E 2 mg/kg/day dissolved in olive oil administered half an hour before the diclofenac sodium by feeding tube per day for 2 weeks. On day 15 all animals were sacrificed with deep ether anesthesia. Their kidneys were removed, fixed in 10% formalin. Representative blocks were taken and embedded in liquid paraffin. For routine histological examination 5 micro m thick section cut by microtome and stained with H and E, PAS and silver methenamine. Renal histology was done under light microscope to see the proximal and distal tubular diameter and count. No significant [P>0.05] changes were observed in the histopathology of kidney tissues of the groups A and C rats. The group B significantly [P<0.001] affected the histopathology of kidney. It may be concluded that diclofenac sodium produces changes in kidney, which may be attributed to ischaemia induced by inhibition of prostaglandin synthesis resulting in tubular necrosis in albino rats simultaneous administration of vitamin-E partially protect the morphological and histological changes induced by diclofenac sodium

Calcium citrate improves the epithelial-to-mesenchymal transition induced by acidosis in proximal tubular cells / Citrato de cálcio melhora a transição epitélio-mesenquimal induzida por acidose em células do túbulo proximal

INTRODUCTION: Epithelial-to-mesenchymal transition (EMT) is a key event in renal fibrosis. The aims of the study were to evaluate acidosis induced EMT, transforming-growth-factor (TGF) β1 role and citrate effect on it. METHODS: HK2 cells (ATCC 2290) were cultured in DMEM/HAM F12 medium, pH 7.4. At 80% confluence, after 24 hr under serum free conditions, cells were distributed in three groups (24 hours): A) Control: pH 7.4, B) Acidosis: pH 7.0 and C) Calcium citrate (0.2 mmol/L) + pH 7.0. Change (Δ) of intracellular calcium concentration, basal and after Angiotensin II (10-6M) exposition, were measured to evaluate cellular performance. EMT was evaluated by the expression of α-smooth muscle actin (α-SMA) and E-cadherin by immunocytochemistry and/or Western blot. TGF-β1 secretion was determined by ELISA in cell supernatant. RESULTS: At pH 7.0 HK2 cells significantly reduced E-cadherin and increased α-SMA expression (EMT). Supernatant TGF-β1 levels were higher than in control group. Calcium citrate decreased acidosis induced EMT and improved cells performance, without reduction of TGF-β production. CONCLUSIONS: Acidosis induces EMT and secretion of TGF-β1 in tubular proximal cells in culture and citrate improves cellular performance and ameliorates acidosis induced EMT.

INTRODUÇÃO: A transição epitélio-mesenquimal (TEM) é um evento chave na fibrose renal. Os objetivos do estudo foram avaliar se o citrato seria capaz de reverter a TEM induzida por acidose, e qual seria o papel do fator de crescimento transformador (TGF) β1 neste evento. MÉTODOS: Células de túbulo proximal (HK2) foram cultivadas em meio DMEM-F12, pH 7,4. Após confluência, as células foram distribuídas em três grupos A) controle: pH 7,4, B) Acidose: pH 7,0 e C) Acidose: pH 7,0 + citrato de cálcio (0,2 mmol/L). A variação na concentração de cálcio intracelular, antes e após a adição de angiotensina II (10-6M) foi medida para avaliar o desempenho celular. TEM foi avaliada pela expressão de α-actina de músculo liso (α-SMA) e E-caderina por imunocitoquímica e/ou de Western blot. A secreção de TGF-β1 foi determinada por ELISA no sobrenadante. RESULTADOS: Em pH 7,0, houve redução significante na expressão de E-caderina e aumento de α-SMA indicando a presença de TEM e a concentração de TGF-β1 foi maior do que no grupo controle. O citrato de cálcio melhorou TEM induzida pela acidose e a resposta das células à angiotensina II, sem redução do TGF-β. CONCLUSÕES: Acidose induz TEM e secreção de TGF-β1 em células tubulares proximais em cultura e o citrato melhora o desempenho celular e a TEM induzida por acidose.

Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury

Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA) on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 çg/mL); CsA (100 µg/mL); sirolimus (50 and 250 çg/mL) + CsA (100 µg/mL); control; vehicle (20 percent ethanol). For in vivo studies, 3-week-old Wistar rats (150-250 g) were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I) in five groups: sham, I, I + SRL (3 mg·kg-1·day-1, po), I + CsA (3 mg·kg-1·day-1, sc), I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR) at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 ± 0.1 mL/min) but not in rats receiving sirolimus + CsA (0.8 ± 0.1 mL/min) despite the reduction in renal blood flow (3.9 ± 0.5 mL/min). Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity.

Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein

Nephrotoxicity is the main side effect of antibiotics such as gentamicin. Preconditioning has been reported to protect against injuries as ischemia/reperfusion. The objective of the present study was to determine the effect of preconditioning with gentamicin on LLC-PK1 cells. Preconditioning was induced in LLC-PK1 cells by 24-h exposure to 2.0 mM gentamicin (G/IU). After 4 or 15 days of preconditioning, cells were again exposed to gentamicin (2.0 mM) and compared to untreated control or G/IU cells. Necrosis and apoptosis were assessed by acridine orange and HOESCHT 33346. Nitric oxide (NO) and endothelin-1 were assessed by the Griess method and available kit. Heat shock proteins were analyzed by Western blotting. After 15 days of preconditioning, LLC-PK1 cells exhibited a significant decrease in necrosis (23.5 ± 4.3 to 6.5 ± 0.3%) and apoptosis (23.5 ± 4.3 to 6.5 ± 2.1%) and an increase in cell proliferation compared to G/IU. NO (0.177 ± 0.05 to 0.368 ± 0.073 ìg/mg protein) and endothelin-1 (1.88 ± 0.47 to 2.75 ± 0.53 pg/mL) production significantly increased after 15 days of preconditioning compared toG/IU. No difference in inducible HSP 70, constitutive HSC 70 or HSP 90 synthesis in tubular cells was observed afterpreconditioning with gentamicin. The present data suggest that preconditioning with gentamicin has protective effects on proximal tubular cells, that involved NO synthesis but not reduction of endothelin-1 or production of HSP 70, HSC 70, or HSP 90. We conclude that preconditioning could be a useful tool to prevent the nephrotoxicity induced by gentamicin.

protective effect of co- supplementation of propolis and vitamin B6 against gentamicin induced nephrotoxicity on proximal tubules in albino rat

Thirty albino rats were used in this work. Rats were divided into five groups, six rats each. Sham control group [Group A] were injected intraperitoneaily, with 5ml of 0.9% NaCI for ten successive days. Gentamicin group [Group B] rats were injected with gentamicin, intraperitoneally, at a dose of 100 mg /kg/day for a period of 10 days. Gentamicin and Vit. B6 group [Group C] rats were injected with gentamicin in the same dose simultaneously with Vit. 36 [2.5 mg/Kg/ day] for ten successive days. Gentamicin and Propolis group [Group D] rats were intraperitoneally injected with same does of gentamicin and propolis 10% solution and given orally by gastric gavage in a dose of 100 mg/kg/day for ten days. Gentamicin, vitamin B6 and propolis group [Group E] rats were injected intraperitoneally with gentamicin, vitamin B6 with the same previous doses and propolis of the same dose orally for ten successive days. On the 11[th] day, the animals were sacrificed. Samples of blood were analyzed for blood urea and serum creatinine. Excised kidneys were fixed in 10% phosphate buffered formalin, dehydrated with ascending grades of ethanol, cleared and, then, embedded in paraffin. The paraffin embedded tissue was cut at 6 Um section and stained with haematoxyline and eosin stains. Small specimens of the kidneys were prepared for ultrathin sections and examined under electron microscope. Gentamicin administration produced a significant increase in serum creatinine [P < 0.001 Vs control] which was avoided by simultaneous vitamin B[6] and propolis treatment for 10 days [P < 0.001]. Vitamin B6 or propolis treatment reduced gentamicin induced elevation in serum creatinine, but still significant over than that of the control by day eleven. The re-suits of the blood urea nitrogen determination were similar. Light microscopic examination of the renal tissues from gentamicin treated rats revealed severe histopathological changes of the proximal convoluted tubules, whereas specimens obtained from group C, or Group D - treated rats revealed only mild changes. In group E rats treated with both vitamin B[6] and propolis, histological examination revealed a normal renal parenchymal picture without any sign of inflammatory or degenerative changes. This finding was further validated by electron microscopic examination. In electron microscopic examination, the cells of the proximal convoluted tubules from group B contained multiple large lysosomes, the mitochondria lost their cristae, some luminal microvilli were disrupted. The protective effect of vitamin B6 against gentamicin-induced nephrotoxicity was supported by electron microscopic examination. While vitamin B6 and propolis-treated rats showed milder histopathological findings similar to that of control. Proximal tubular epithelial cells were regaining normal structure. In a few areas, the tubular cells were lower with few organelles and rudimentary villi. There was little protection by propolis alone against the nephrotoxic effects of gentamicin treatment. The present study could conclude that co-administration of vitamin B6 and propolis has beneficial effects on renal preservation in gentamicin induced nephrotoxicity

Histological study on the effect of tobramycin dosage regimens on renal proximal tubular cells in the rats

The present study was undertaken to show the potential nephrotoxicity of tobramycin, given in two different dosage regimens, on the proximal convoluted tubules by using the light and transmission electron microscopic techniques. Thirty-five rats were divided into three groups: Group I served as control, Group II received tobramycin at 4mg/Kg of body weight intraperitoneally every 8 hours for ten days, and Group III received once-daily dosing of intraperitoneal injection of tobramycin at 12mg/Kg of body weight for ten days. The rats were sacrificed 3 days after the last injection. Small pieces of the right kidneys of all the animals were processed for light and electron microscopic examination. The study showed that tobramycin resulted in certain structural and ultrastructural changes in the proximal convoluted tubules. These changes included vacuolar degeneration in the epithelial cells, increased number of lysosomes with variably sized myeloid bodies, mitochondrial oedema, and loss of apical microvilli. These changes were clearly evident following multiple-daily dosing and were less obvious following once-daily dosing. Furthermore, regenerating tubular epithelial cells were evident following once-daily dosing administration. The experimental tobramycin toxicity can be reduced by administering equivalent amounts of the antibiotic in a once-daily dosing as opposed to multiple-daily injections. It is hoped that this study will contribute in the selection of a more appropriate dosing regimen for tobramycin in human beings

Gentamicin Induced Apoptosis of Renal Tubular Epithelial (LLC-PK1) Cells

Nephrotoxicity is a major limiting factor in the use of aminoglycoside antibiotics, the mechanisms for which are still speculative. To clarify the mechanisms of renal tubular cell death induced by aminoglycosides, we examined the renal proximal tubule-like cell line, LLC-PK1, after inducing apoptosis through a chronic treatment with gentamicin (GM). Changes in the expression of the Fas were also investigated. On flow cytometric analysis, 5.7 +/- 3.3% of the control cells appeared in a region of decreased forward light scatter and increased side light scatter, where both indices represent the characteristics of apoptotic cell death. Compared to the control, treatment with 10 mM of GM for 15 days significantly increased the proportion of cells in the apoptotic region to 23.9 +/- 8.5%. This finding was supported by electrophoretic analysis of the DNA extracted from the GM-treated cells, where a series of bands corresponding to integer multiples of 180 to 200 base pairs was visualized. However, the 15-day GM treatment did not cause a significant elevation in the expression of the 45 kD Fas protein, the cell surface molecule that stimulates apoptosis, by Western blot analysis. In conclusion, long-term exposure to GM induces apoptosis of the renal tubular epithelial cells, and this process may contribute to some of the aminoglycoside nephrotoxicities. Further studies are needed on the mechanism(s) of apoptosis induced by GM.

Effects of monensin on glycosphingolipid metabolism in cultured human proximal tubular cells.

Effects of monensin, a monovalent cationic ionophore which disrupts Golgi apparatus and its related functions, on glycosphingolipid (GSL) metabolism were investigated in cultured human proximal tubular (PT) cells. Monensin (10(-6) M) stimulated [3H]Gal incorporation into GlcCer, GalCer and LacCer by 8.5-fold and 15-fold, respectively, in PT cells as compared to control. In contrast, [3H]Gal incorporation into GbOse3Cer and GM3 remained unchanged and that into GbOse4Cer was decreased 2-fold as compared to control. GSL measured by HPLC revealed that in cells incubated with monensin, GlcCer, GalCer and LacCer levels were increased 1.6-fold and 7-fold, respectively, whereas GbOse3Cer and GbOse4Cer levels were decreased several folds. Cells incubated with monensin contained 2.5- to 3-fold higher activity of alpha-galactosidase, beta-galactosidase and beta-glucosidase than control, whereas the activity of UDP-gal: glucosylceramide galactosyltransferase (beta-GalT-2) was 8-fold lower than control cells. Cells incubated with monensin took up and degraded one-half as much 125I-LDL as that of control cells. In control cells, exogenously derived [3H]LacCer on LDL was rapidly taken up and catabolized to monoglycosylceramide, or it was used for the endogenous synthesis of globotriosylceramide (trihexosylceramide), globotetraosylceramide (tetrahexosylceramide) and a ganglioside, GM3. In contrast, cells incubated with monensin accumulated most of the [3H]LacCer-LDL. Exogenously derived [3H]LacCer on LDL was catabolized to GlcCer, but was not utilized, for the synthesis of globotriosylceramide, globotetraosylceramide and GM3 in cells incubated with monensin.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of propranolol and nifedipine on in vitro fluid absorption by the isolated perfused proximal convoluted tubule of the rabbit

The inhibition of fluid absorption (Jv) by the antiarrhythmic and antihypertensive drugs propranolol and nifedipine, which increase cytosolic Ca*+ concentration, was studied using the isolated rabbid proximal convoluted tubule perfused in vitro. Proximal convuluted tubules were perfused and bathed with a modified Krebs-Henseleit solution containing bovine serum albumin. Jv was measured after a 30-min control period, after 40 min with eithe 0.1 mM propranolol or 1.0 mM mifedipine on the peritubular side and after a 40-min recovery period. Both drugs inhibited Jv (58% propranolol, and 21% nifedipine) The 40-min recovery period was sufficient to reserve the effect of nifedipine, but propranolol-treated tubules (N=6) only reached 78% of the control Jv value. These results demonstrate that antiarrhythmic and anthypertensive drugs are powerful inhbitors of net fluid absorption by exerting a direct effect on proximal or distal tubule cells, thus acting like "local diuretics"

Estudio morfométrico de riñones de ratas tratadas con propranolol / Morphometric study of kidneys of rats treated with propranolol

Se realiza un estudio morfométrico de riñones de ratas tratadas con propranolol. Ratas blancas recibieron propranolol (en solución de 0,15 mg/ml de suero fisiológico) en dos inyecciones intraperitoneales diarias de 0,5 ml/100 gr de peso corporal durante 10 y 20 días según los grupos. Otros animales recibieron propranolol, en forma similar, más la simultánea administración de estrés eléctrico, (pulsos de 40 voltios de 1 s cada 3 min y durante 9 horas diarias en el piso de las jaulas). Los animales controles, sólo recibieron inyecciones intraperitoneales de suero fisiológico. Se observó crecimiento renal principalmente con aumento del volumen tubular proximal y agrandamiento glomerular en las ratas que recibieron propranolol solamente. Cuando el tratamiento fue acompañado de estrés, no fue observado crecimiento alguno. Se sugiere que los resultados puedan deberse a una acción vasodilatadora del propranolol sobre los vasos intrarrenales, mediante la posible disminución de la actividad de renina plasmática, con la consiguiente sobrecarga de filtración e hipertrofia tubular por incremento del trabajo reabsortivo