Antioxidant treatment reverts increased arterial basal tone and oxidative stress in nephrectomized (5/6) hypertensive rats

Nonischemic 5/6 nephrectomized rat (NefR) is a model of chronic kidney disease. However, little is known about vascular dysfunction and its relation with hypertension in NefR. Aims. To evaluate possible alterations of endothelial function, NObioavailability, and basal tone in aorta from NefR and the role of oxidative stress. Sprague Dawley rats were divided into sham rats (SR), NefR, and NefR treated with tempol (NefR-T). Mean arterial pressure (MAP) and renal function were determined. In isolated aortic rings the following was measured: 1-endothelial function, 2-basal tone, 3-NO levels, 4-membrane potential (MP), and 5-oxidative stress. NefR increased MAP (SR: 119 ± 4 mmHg; =7; NefR: 169 ± 6; =8; < 0.001). Tempol did not modify MAP (NefR-T: 168 ± 10; =6; < 0.001). NefR showed endothelial dysfunction, increased basal tone and decreased NO levels (SR: 32 ± 2 nA; =7, NefR: 10 ± 2; =8; < 0.001). In both in vitro and in vivo tempol improves basal tone, NO levels, and MP. Oxidative stress in NefR was reverted in NefR-T. We described, for the first time, that aorta from NefR presented increased basal tone related to endothelial dysfunction and decreased NO-bioavailability. The fact that tempol improves NO-contents and basal tone, without decrease MAP, indicates that oxidative stress could be implicated early and independently to hypertension, in the vascular alterations.Fil: Marañón, Rodrigo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucuman. Instituto Superior de Investigaciones Biologicas; Argentina. University Of Mississippi; Estados UnidosFil: Joo Turoni, Claudio Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucuman. Instituto Superior de Investigaciones Biologicas; ArgentinaFil: Karbiner, María Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucuman. Instituto Superior de Investigaciones Biologicas; ArgentinaFil: Salas, Nicolás Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucuman. Instituto Superior de Investigaciones Biologicas; ArgentinaFil: Peral, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucuman. Instituto Superior de Investigaciones Biologicas; Argentin

Vascular hyporeactivity to angiotensin II and noradrenaline in a rabbit model of obesity

This study was conducted to explore the vascular reactivity of angiotensin II and noradrenaline and their relationship with endothelial function in rabbits fed a high-fat diet (HFD). The animals were fed either an HFD or regular chow [control diet (CD)]. After 12 weeks, the rabbits fed the HFD showed higher blood pressure, body weight, and insulin levels. Glucose tolerance was impaired and positively related to blood pressure. An endothelium-independent decrease of the sensitivity to angiotensin II [pD 2 endothelium-intact aortic rings (E+) in CD: 8.02 ± 0.07 vs. HFD: 7.60 ± 0.01; pD 2 endothelium-removed aortic rings (E-) in CD: 8.16 ± 0.11 vs. HFD: 7.83 ± 0.16] and noradrenaline (pD 2 E+ in CD: 6.36 ± 0.06 vs. HFD: 5.29 ± 0.06; pD 2 E- in CD: 6.11 ± 0.08 vs. HFD: 5.80 ± 0.08) was found. Noradrenaline desensitized the angiotensin II response (pD 2 with noradrenaline pretreatment in E+: 7.03 ± 0.16; in E-: 7.10 ± 0.02), but angiotensin II did not change the noradrenaline response. Acetylcholine maximal relaxation and basal nitric oxide (NO) release were comparable in both diet groups. The efficacy of angiotensin II (R max CD: 4604 ± 574 mg vs. HFD: 3251 ± 533 mg) and noradrenaline (R max CD: 11,675 ± 804 mg vs. HFD: 7975 ± 960 mg) was reduced in E+. L-N G-nitroarginine methyl ester (L-NAME) recovered the efficacy of noradrenaline (R max L-NAME: 12,015 ± 317 mg). In contrast, L-NAME had no effect on the angiotensin II response. Noradrenaline enhanced NO levels, but angiotensin II did not. Therefore, NO was associated with hyporeactivity to noradrenaline. The resting potential was more negative in E+, and the endothelium diminished the angiotensin II-induced depolarization. These findings demonstrated that the crosstalk and the endothelium may induce hyporeactivity to angiotensin II and noradrenaline as a mechanism to compensate the increase in the blood pressure in HFD-induced obesity.Fil: Jerez, Susana Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Scachi, Fabricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Sierra, Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Karbiner, María Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Peral, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

High fat diet induces microvesicular steatosis in an experimental model of metabolic syndrome without dislipidemia

La enfermedad del hígado graso no alcohólico (NAFLD) inducida por dietas ricas en grasas es considerada actualmente el componente hepático del síndrome metabólico, sin embargo su fisiopatología es actualmente objeto de controversia. El objetivo del presente estudio fue evaluar los cambios morfológicos hepáticos y su relación con componentes del síndrome metabólico en un modelo de conejo alimentado con una dieta rica en grasas. Los animales (n=24) fueron separados en dos grupos: uno recibió una dieta control (DC, n=12) y el otro una DC enriquecida con grasa al 10 % (DG, n=12) durante 12 semanas. Al final del periodo de alimentación se realizaron test de tolerancia a la glucosa y determinaciones de presión arterial media (PAM), frecuencia cardiaca (FC), insulina, colesterol total, HDL-C, LDL-C, triglicéridos, sustancias reactivas del ácido tiobarbitúrico (TBARS) y relación glutatión reducido/oxidado (GSH/GSSH). Se extrajeron grasas de la zona visceral abdominal y el hígado y se pesaron. Se realizó análisis histológico de cortes de hígado. Los conejos alimentados con DG presentaron aumento de peso corporal, de grasa visceral abdominal, de PAM, FC, insulina plasmática. No se observaron diferencias en los lípidos, TBARS ni GSH/GSSH con respecto a los DC. El análisis histológico mostró la presencia de esteatosis microvesicular. En conclusión, una DG generó un modelo de síndrome metabólico caracterizado por una alteración temprana hepática compatible con esteatosis microvesicular. Considerando que en este modelo los niveles de lípidos plasmáticos y los parámetros de estrés oxidativo fueron normales, la resistencia a la insulina sería el biomarcador temprano de NAFLD en el síndrome metabólico.High fat diet induces non-alcoholic fatty liver disease that is now considered to be the hepatic component of the metabolic syndrome. However, its physiophatology remains a controversial subject. The present study was carried out to evaluate morphological changes in the liver and its association with known components of metabolic syndrome in a rabbit model. Animals (n=24) were fed either on regular chow (CD; n=12) or high fat diet 10 % (HFD, n=12). After 12 weeks, body weight, visceral abdominal fat, glucose tolerance test, mean arterial blood pressure and heart rate were significantly increased in rabbits fed on HFD. Plasma levels of total cholesterol, LDLcholesterol, HDL-cholesterol, triglycerides, glutathione reduced/glutathione oxidized ratio and thiobarbituric acid reactive substances were similar in both diet groups. Insulin from plasma and HOMA index were higher in rabbis fed on HFD. Histological analysis showed hepatic microvesicular steatosis in this obesity model. In conclusion, HFD induced together with metabolic alterations characterizing the metabolic syndrome early liver injury compatible with microvesicular steatosis. Considering that in such conditions triglycerides levels and oxidative parameters were similar to controls, insulin resistance may be the earlier biomarker of liver injury in the metabolic syndrome.Fil: Scacchic, Fabricio. Universidad Nacional de Tucumán. Facultad de Medicina; ArgentinaFil: Karbiner, María Sofía. Universidad Nacional de Tucumán. Facultad de Medicina; ArgentinaFil: Pucci Alcaide, Franco Jose. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Peral, Maria de Los Angeles. Universidad Nacional de Tucumán. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Jerez, Susana Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentin

The role of oxidative stress in alterations of hematological parameters and inflammatory markers induced by early hypercholesterolemia

Aims: The investigation of the effects of a high cholesterol diet (HD) for a short-time period on hematological parameters and the potential role of oxidative stress and inflammation markers. Main methods: Rabbits were fed either a control diet or a diet containing 1% cholesterol (HD) for 5–6 weeks. The plasma lipid levels, C reactive protein (CRP), total red blood cells (RBC), total white blood cells (WBC), platelet count, packed cell volume (PCV) and leukocyte formula were determined. Oxidative stress was evaluated by the thiobarbituric acid reactive substances (TBARS), total glutathione and GSH serum level measurements. The osmotic fragility and the membrane fluidity of erythrocytes were determined. The levels of total cholesterol and TBARS were also measured in the erythrocyte membrane suspension. Key findings: A decrease in the RBC and PCV was observed in rabbits fed on HD. The membrane rigidity and osmotic fragility were increased, and the morphological changes caused by the HD and TBARS levels in the erythrocyte membrane may account for this phenomenon. The inflammatory markers as the CRP levels, the platelet count, the WBC and the neutrophils were increased. The TBARS and GSH levels in the serum were increased and decreased, respectively. Significance: This study shows that feeding rabbits an HD for a short time induces hematological alterations, disturbances in the oxidant–antioxidant balance and an increase of inflammatory markers. These findings support the importance of the early correction or prevention of high cholesterol levels to disrupt the process leading to the development of cardiovascular diseases.Fil: Karbiner, María Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucuman. Instituto Superior de Investigaciones Biologicas; ArgentinaFil: Sierra, Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucuman. Instituto Superior de Investigaciones Biologicas; ArgentinaFil: Minahk, Carlos Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucuman. Instituto Superior de Investigaciones Biologicas; ArgentinaFil: Fonio, Maria Cristina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; ArgentinaFil: Peral, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucuman. Instituto Superior de Investigaciones Biologicas; ArgentinaFil: Jerez, Susana Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucuman. Instituto Superior de Investigaciones Biologicas; Argentin

Tempol blunts afferent arteriolar remodeling in chronic nitric oxide-deficient hypertension without normalizing blood pressure

Renal preglomerular vessels play a central role in modulating renal function and injury, especially during conditions of renal hemodynamic stress such as hypertension. We evaluated whether improving the balance between nitric oxide (NO) and oxidative stress improves the morphological alterations of renal afferent arterioles that occur in NO deficiencyinduced hypertension. We measured indices of NO and oxidative stress and evaluated renal morphology and afferent arteriolar remodeling in rats treated with vehicle, L-NAME or L-NAME plus tempol (a superoxide dismutase mimetic) for 6 weeks. L-NAME-treated rats had hypertension, lower urinary and renal NO indices, higher renal cortical levels of TBARS, GSSG and GSSG/GSH. This was associated with significant eutrophic inward remodeling of the afferent arterioles; they had a marked decrease in arteriolar lumen area and a striking increase in arteriolar wall thickness and media to lumen ratio. Tempol did not significantly reduce blood pressure, but increased NO levels, decreased oxidative stress and partially blunted L-NAME-induced remodeling of afferent arterioles. L-NAME-induced remodeling of afferent arterioles is blunted by tempol. This beneficial effect on remodeling is associated with increases in NO indices, decreases in oxidative stress, without significant decreases in blood pressure. Thus, the balance between these components may contribute to the altered renal hemodynamics and function in this model.Fil: Marañón, Rodrigo Oscar. University of Mississippi; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucuman. Facultad de Medicina. Departamento Biomedico. Laboratorio de Fisiología y Farmacología Vascular; ArgentinaFil: Juncos, Luis A.. University of Mississippi; Estados UnidosFil: Joo Turoni, Claudio Martín. Universidad Nacional de Tucuman. Facultad de Medicina. Departamento Biomedico. Laboratorio de Fisiología y Farmacología Vascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Karbiner, María Sofía. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Romero, Damián Gastón. University of Mississippi; Estados UnidosFil: Peral, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucuman. Facultad de Medicina. Departamento Biomedico. Laboratorio de Fisiología y Farmacología Vascular; Argentin