Browsing by Subject "Renal function"

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    Age- and Sodium-Sensitive Hypertension and Sex-Dependent Renal Changes in Rats With a Reduced Nephron Number
    (American Heart Association, 2008-02-07) Salazar, Francisco; Reverte, Virginia; Saez, Fara; Lorai, Analia; Llinas, Maria Teresa; Salazar, F. Javier; Fisiología
    We have demonstrated that the reduction of angiotensin II effects during the nephrogenic period reduces the nephron number and induces the development of hypertension. The hypotheses examined are that this reduction of angiotensin effects leads to the development of an age-dependent sodium sensitive hypertension and that the hypertension is angiotensin II dependent. Newborn rats were treated with an angiotensin II type 1 receptor antagonist during the first 2 weeks of age. At 3 to 4 and 11 to 12 months of age, changes in systolic blood pressure, proteinuria, and renal function in response to a prolonged high sodium intake were examined. The basal blood pressure response to the administration of the angiotensin II receptor antagonist was also evaluated at both ages. Basal blood pressure was similarly elevated (P<0.05) in male and female treated rats, and the increment was age dependent. High sodium intake only elicited a blood pressure elevation (136±1 to 154±3 mm Hg; P<0.05) and a decrease in glomerular filtration rate (28%; P<0.05) at 11 to 12 months in treated rats. Blockade of angiotensin II receptors during renal development induced an increase (P<0.05) in proteinuria that was age and sex dependent, but high sodium intake only induced an elevation in proteinuria in the younger rats (50%; P<0.05). Hypertension was maintained by angiotensin II at both ages because blood pressure decreased to normal levels after treatment with an angiotensin II type 1 receptor antagonist. This study shows that the reduction of angiotensin II effects during the nephrogenic period modifies renal function and induces the development of an angiotensin II–dependent hypertension that becomes sodium sensitive during aging.
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    Aminopeptidases in Cardiovascular and Renal Function. Role as Predictive Renal Injury Biomarkers
    (MDPI, 2020-08-05) Vargas, Félix; Wangesteen, Rosemary; Rodríguez-Gómez, Isabel; García-Estañ, Joaquín; Fisiología
    Aminopeptidases (APs) are metalloenzymes that hydrolyze peptides and polypeptides by scission of the N-terminus amino acid and that also participate in the intracellular final digestion of proteins. APs play an important role in protein maturation, signal transduction, and cell-cycle control, among other processes. These enzymes are especially relevant in the control of cardiovascular and renal functions. APs participate in the regulation of the systemic and local renin–angiotensin system and also modulate the activity of neuropeptides, kinins, immunomodulatory peptides, and cytokines, even contributing to cholesterol uptake and angiogenesis. This review focuses on the role of four key APs, aspartyl-, alanyl-, glutamyl-, and leucyl-cystinyl-aminopeptidases, in the control of blood pressure (BP) and renal function and on their association with different cardiovascular and renal diseases. In this context, the effects of AP inhibitors are analyzed as therapeutic tools for BP control and renal diseases. Their role as urinary biomarkers of renal injury is also explored. The enzymatic activities of urinary APs, which act as hydrolyzing peptides on the luminal surface of the renal tubule, have emerged as early predictive renal injury biomarkers in both acute and chronic renal nephropathies, including those induced by nephrotoxic agents, obesity, hypertension, or diabetes. Hence, the analysis of urinary AP appears to be a promising diagnostic and prognostic approach to renal disease in both research and clinical settings.
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    COX2 inhibition during nephrogenic period induces ANG II hypertension and sex-dependent changes in renal function during aging
    (American Physiological Society, 2014-03-01) Reverte, Virginia; Tapia, Antonio; Loria, Analia; Salazar, Francisco; Llinas Más, María Teresa; Salazar, Francisco Javier; Fisiología
    This study was performed to test the hypothesis that ANG II contributes to the hypertension and renal functional alterations induced by a decrease of COX2 activity during the nephrogenic period. It was also examined whether renal functional reserve and renal response to volume overload and high sodium intake are reduced in 3–4- and 9–11-mo-old male and female rats treated with vehicle or a COX2 inhibitor during nephrogenic period (COX2np). Our data show that this COX2 inhibition induces an ANG II-dependent hypertension that is similar in male and female rats. Renal functional reserve is reduced in COX2np-treated rats since their renal response to an increase in plasma amino acids levels is abolished, and their renal ability to eliminate a sodium load is impaired (P < 0.05). This reduction in renal excretory ability is similar in both sexes during aging but does not induce the development of a sodium-sensitive hypertension. However, the prolonged high-sodium intake at 9–11 mo of age leads to a greater proteinuria in male than in female (114 ± 12 μg/min vs. 72 ± 8 μg/min; P < 0.05) COX2np-treated rats. Renal hemodynamic sensitivity to acute increments in ANG II is unaltered in both sexes and at both ages in COX2np-treated rats. In summary, these results indicate that the reduction of COX2 activity during nephrogenic period programs for the development of an ANG II-dependent hypertension, reduces renal functional reserve to a similar extent in both sexes, and increases proteinuria in males but not in females when there is a prolonged increment in sodium intake.
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    Effect of unilateral nephrectomy on renal function of diabetic rats
    (Murcia : F. Hernández, 2004) Lopes, G.S.; Lemos, C.C.S.; Mandarim-de-Lacerda, Carlos A.; Bregman, R.
    Glomerular alterations of experimental diabetes mellitus are observed in animals submitted to a reduction in renal mass, suggesting that some mechanisms responsible for the progression of renal disease are common. The aim of this study was to investigate the effect of nephrectomy on the renal function and morphology of diabetic rats. Male Wistar rats were divided into 4 groups: control (C), n=8; diabetic (DM), n=8; non-diabetic nephrectomized (Nx), n=8; (DMNx), n=9. DM was induced by streptozotocin (65mg/Kg), and animals were treated with insulin. After 12 weeks, the glomerular filtration rate (GFR), renal plasma flow (RPF) and mean arterial pressure (MAP) were evaluated in unanaesthetized animals. Glomerular volume (GV), glomerular sclerosis index (GSI), mesangial volume density (Vvmes) and glomerular capillary surface density (Svcap) were also evaluated. Results show that kidney weight increased in Nx groups, being higher in DMNx. GFR was higher in Nx groups as was RPF, being higher in DMNx. RVR was lower in Nx groups, especially in DMNx. MAP was not different among the groups. RPF and GFR showed a high correlation for the DMNx group (r=0.95, p=0.02). The DMNx group showed a correlation between RVR and GFR (r=-0.96, p=0.005). The GV increased in Nx groups, and the GSI was higher in DMNx. Vvmes and Svcap increased in DMNx group. In summary, Nx groups developed similar degrees of glomerular hypertrophy, but only DMNx showed an increased value for GSI. The present data suggest that the acceleration of glomerular lesions in DMNx animals was more closely associated to hemodynamic adaptations than to glomerular hypertrophy.
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    Función renal a largo plazo en supervivientes de tumor de Wilms
    (Sociedad Española de Cirugía Pediátrica, 2019) Sánchez-Sánchez, A.; Girón Vallejo, Óscar; Ruiz Pruneda, R.; Fernández Ibieta, M.; Villamil, V.; Giménez Aleixandre, M.C.; Montoya-Rangel, C.A.; Fuster Soler, José Luis; Pascual Gázquez, J.F.; Ortega García, Juan Antonio; Hernández Bermejo, Juan Pedro; Cirugía, Pediatría y Obstetricia y Ginecología; Facultad de Medicina
    Objetivos. Evaluar la función renal y la morbimortalidad a largo plazo, en supervivientes de tumor de Wilms (TW) no sindrómico. Material y métodos. Estudio retrospectivo de pacientes con TW entre 1993-2017 tratados según protocolos SIOP. Evaluamos mortalidad, filtrado glomerular (FG), prevalencia de hipertensión arterial (HTA), necesidad de diálisis y trasplante renal. Se definió enfermedad renal crónica (ERC) como FG <90 ml/min/1,73 m2. Resultados. En los 25 años analizados se trataron 39 pacientes con edad media diagnóstica de 3,6 años (0,3-11 años). Mediana de seguimiento 6 años (0,5-21 años). El 48% (19 pacientes) debutaron con estadio I o II. Cuatro pacientes presentaron histología de alto riesgo (10%). La mortalidad fue del 10%. El 16% (6 pacientes) desarrolló ERC (grados I-II). Ningún paciente precisó terapia renal sustitutoria (TRS) o trasplante. La presencia de ERC tanto en enfermedad unilateral como bilateral fue del 16%, p>0,05; OR 1,04 (IC 95% 0,09-10,9). Se obtuvieron idénticos resultados (16%) comparando pacientes que recibieron radioterapia frente a aquellos que no. Los pacientes en estadio I, II y III presentaron una prevalencia de ERC del 11% vs. 40% en estadio IV (p=0,12); OR 5,3 (IC 95% 0,61-45). Ningún paciente asoció HTA crónica. Conclusiones. En el presente estudio la prevalencia de ERC en supervivientes de TW no sindrómico es baja pero no desdeñable, aunque ninguno precisó trasplante renal o TRS. La presencia de enfermedad bilateral y la radioterapia no se asociaron al desarrollo de ERC. La enfermedad metastásica condiciona un riesgo mayor de ERC.
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    Role of angiotensin II in arterial pressure and renal hemodynamics in rats with altered renal development: age- and sex-dependent differences
    (2013-01-01) Reverte, Virginia; Tapia, Antonio; Baile, Goretti; Gambini, Juan; Giménez, Ignacio; Llinas, María Teresa; Salazar, F. Javier; Fisiología
    Numerous studies have demonstrated that angiotensin II (ANG II) is involved in hypertension and renal changes occurring as a consequence of an adverse event during renal development. However, it was unknown whether this involvement is sex and age dependent. This study examines whether the increments in arterial pressure (AP) and in the renal sensitivity to ANG II are sex and age dependent in rats with altered renal development. It also evaluates whether the ANG II effects are accompanied by increments in AT1 receptors and oxidative stress. Experiments were performed in 3- to 4- and 10- to 11-mo-old rats treated with vehicle or an AT1 receptor antagonist (ARAnp) during the nephrogenic period. ARAnp-treated rats were hypertensive, but an age-dependent rise in AP was only found in males. Three days of treatment with candesartan (7 mg·kg−1·day−1) led to a fall of AP that was greater (P < 0.05) in male than in female 10- to 11-mo-old ARAnp-treated rats. Oxidated proteins were elevated (P < 0.05), and the decrease in AP elicited by candesartan was reduced (P < 0.05) when these rats are also treated with tempol (18 mg·kg−1·day−1). Hypertension was not maintained by an elevation of AT1 receptors in kidneys and mesenteric arteries. The acute renal hemodynamic response to ANG II (30 ng·kg−1·min−1) was similarly enhanced (P < 0.05) in both sexes of ARAnp-treated rats at 3–4 but not at 10–11 mo of age. Our results suggest that an adverse event during the nephrogenic period induces an ANG II-dependent increment in AP that is aggravated only in males during aging and that oxidative stress but not an increase in AT1 receptor contributes to the rise in AP. This study also shows that the renal hemodynamic sensitivity to ANG II is transitorily enhanced in both sexes of rats with altered renal development.
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    Sex-dependent differences in the adverse renal changes induced by an early in life exposure to a high-fat diet.
    (2019-02-01) Moreno Ayuso, Juan Manuel; Tapia, Antonio; Reverte, Virginia; Oltra, Lidia; Llinás Más, María Teresa; Salazar, Francisco Javier; Martínez Cáceres, Carlos Manuel; Fisiología
    This study examines whether the intake of a high-fat diet very early in life leads to changes in arterial pressure and renal function and evaluates whether the mechanisms involved in these changes are sex-dependent. Experiments were performed in male and female Sprague-Dawley rats fed a normal or high-fat diet from weaning to 4 mo of age. This exposure to a high-fat diet lead to an angiotensin II-dependent elevation in arterial pressure and to significant increments in fat abdominal volume and plasma leptin that were similar in both sexes. In addition, the angiotensin II-induced increment in renal vascular resistance was greater ( P < 0.05) in male (106 ± 14%) and female (97 ± 15%) rats fed a high-fat diet than in rats fed a normal-fat diet (51 ± 8%). However, the high-fat intake during early life induced increments in albuminuria, interleukin-6, and infiltration of CD3 lymphocytes in the renal parenchyma that were greater ( P < 0.05) in male than in female rats. Other sex-dependent differences in response to high-fat intake were that adiponectin levels only decreased in females (21%, P < 0.05), and renal NF-κB expression only increased in males (31%, P < 0.05). In summary, the early exposure to a high-fat diet leads to angiotensin II-dependent arterial pressure elevations and to increments in abdominal fat and in the renal sensitivity to angiotensin II that are similar in both sexes. However, the mechanisms involved in the renal changes associated with early exposure to a high-fat diet are different in males and females.