[Effect of nutritional status on mortality and functional recovery in older adults with hip fracture]. / Efecto del estado nutricional en la mortalidad y recuperación funcional en adultos mayores con fractura de cadera.

INTRODUCTION: Malnutrition is a common problem in the elderly population but has not been fully studied in elderly people with hip fractures. The goal is to estimate annual mortality based on nutrition in the elderly with hip fracture and compare motor functionality. MATERIAL AND METHODS: Retrospective cohort of patients over 65 years of age with hip fracture included in the Institutional Register of The Elderly with Hip Fracture of a University Hospital, between July 2014 and July 2018. Nutritional status with Mini Nutritional Assessment Short-Form (MNA-SF) was assessed at hospital admission. Motor functional capacity was evaluated with Parker Scale (PS) basal, at three and 12 months. RESULTS: 1,253 patients were included. 49.92% (CI95% 47.12-52.72) were malnourished. The annual mortality of the well-nourished (WN) was 9.45% (CI95% 7.23-12.30) against 21.52% (CI95% 18.12-25.45; p 0.001) of the malnourished (MN). The risk of death was associated with malnutrition HR 2.45 (CI95% 1.75-3.43; p 0.001). After adjusting it by age, sex, fragility, AVD, Charlson comorbility index and dementia, the risk remained HR 1.71 (CI95% 17-2.49; p = 0.005). With respect to functionality, the basal Parker Scale median (EP) for the WN group was 9 (RIC6-9) and for MN was 5 (RIC3-9) p 0.001, 6 months (RIC3-6) and 4 (RIC2-6) p 0.001 and 12 months 6 (RIC4-7) and 3 (RIC2-6) p 0.001. CONCLUSIONS: There is an association between the malnutrition of the elderly with hip fracture and its mortality with a year of evaluation; we also find a difference in motor functionality.

INTRODUCCIÓN: La malnutrición es una problemática frecuente en la población anciana, pero no ha sido completamente estudiado en ancianos con fractura de cadera. El objetivo es estimar mortalidad anual según nutrición en ancianos con fractura de cadera y comparar la funcionalidad motora. MATERIAL Y MÉTODOS: Cohorte retrospectiva de pacientes mayores de 65 años con fractura de cadera incluidos en el Registro Institucional de Ancianos con Fractura de Cadera de un Hospital Universitario, entre Julio de 2014 y Julio de 2018. Se evaluó el estado nutricional con Mini Nutritional Assessment Short-Form (MNA-SF) al ingreso hospitalario. La capacidad funcional motora fue evaluada con escala de Parker (EP) basal, a los tres y 12 meses. RESULTADOS: Se incluyeron 1,253 pacientes. 49.92% (IC95% 47.12-52.72) estaba malnutrido. La mortalidad anual de los bien nutridos (BN) fue de 9.45% (IC95% 7.23-12.30) contra 21.52% (IC95% 18.12-25.45; p 0.001) de los malnutridos (MN). El riesgo de muerte se asoció a la malnutrición HR 2.45 (IC95% 1.75-3.43; p 0.001). Luego de ajustarlo por edad, sexo, fragilidad, AVD, índice de comorbilidades de Charlson y demencia, el riesgo se mantuvo HR 1.71 (IC95% 17-2.49; p = 0.005). Con respecto a la funcionalidad, la mediana de la escala de Parker (EP) basal para el grupo BN fue 9 (RIC6-9) y para MN fue 5 (RIC3-9) p 0.001, a los tres meses 6 (RIC3-6) y 4 (RIC2-6) p 0.001 y a los 12 meses 6 (RIC4-7) y 3 (RIC2-6) p 0.001. CONCLUSIONES: Existe asociación entre la malnutrición del anciano con fractura de cadera y su mortalidad al año, asimismo una diferencia en la funcionalidad motora.

Efecto del estado nutricional en la mortalidad y recuperación funcional en adultos mayores con fractura de cadera / Effect of nutritional status on mortality and functional recovery in older adults with hip fracture

Resumen: Introducción: La malnutrición es una problemática frecuente en la población anciana, pero no ha sido completamente estudiado en ancianos con fractura de cadera. El objetivo es estimar mortalidad anual según nutrición en ancianos con fractura de cadera y comparar la funcionalidad motora. Material y métodos: Cohorte retrospectiva de pacientes mayores de 65 años con fractura de cadera incluidos en el Registro Institucional de Ancianos con Fractura de Cadera de un Hospital Universitario, entre Julio de 2014 y Julio de 2018. Se evaluó el estado nutricional con Mini Nutritional Assessment Short-Form (MNA-SF) al ingreso hospitalario. La capacidad funcional motora fue evaluada con escala de Parker (EP) basal, a los tres y 12 meses. Resultados: Se incluyeron 1,253 pacientes. 49.92% (IC95% 47.12-52.72) estaba malnutrido. La mortalidad anual de los bien nutridos (BN) fue de 9.45% (IC95% 7.23-12.30) contra 21.52% (IC95% 18.12-25.45; p ≤ 0.001) de los malnutridos (MN). El riesgo de muerte se asoció a la malnutrición HR 2.45 (IC95% 1.75-3.43; p ≤ 0.001). Luego de ajustarlo por edad, sexo, fragilidad, AVD, índice de comorbilidades de Charlson y demencia, el riesgo se mantuvo HR 1.71 (IC95% 17-2.49; p = 0.005). Con respecto a la funcionalidad, la mediana de la escala de Parker (EP) basal para el grupo BN fue 9 (RIC6-9) y para MN fue 5 (RIC3-9) p < 0.001, a los tres meses 6 (RIC3-6) y 4 (RIC2-6) p ≤ 0.001 y a los 12 meses 6 (RIC4-7) y 3 (RIC2-6) p < 0.001. Conclusiones: Existe asociación entre la malnutrición del anciano con fractura de cadera y su mortalidad al año, asimismo una diferencia en la funcionalidad motora.

Abstract: Introduction: Malnutrition is a common problem in the elderly population but has not been fully studied in elderly people with hip fractures. The goal is to estimate annual mortality based on nutrition in the elderly with hip fracture and compare motor functionality. Material and methods: Retrospective cohort of patients over 65 years of age with hip fracture included in the Institutional Register of The Elderly with Hip Fracture of a University Hospital, between July 2014 and July 2018. Nutritional status with Mini Nutritional Assessment Short-Form (MNA-SF) was assessed at hospital admission. Motor functional capacity was evaluated with Parker Scale (PS) basal, at three and 12 months. Results: 1,253 patients were included. 49.92% (CI95% 47.12-52.72) were malnourished. The annual mortality of the well-nourished (WN) was 9.45% (CI95% 7.23-12.30) against 21.52% (CI95% 18.12-25.45; p ≤ 0.001) of the malnourished (MN). The risk of death was associated with malnutrition HR 2.45 (CI95% 1.75-3.43; p ≤ 0.001). After adjusting it by age, sex, fragility, AVD, Charlson comorbility index and dementia, the risk remained HR 1.71 (CI95% 17-2.49; p = 0.005). With respect to functionality, the basal Parker Scale median (EP) for the WN group was 9 (RIC6-9) and for MN was 5 (RIC3-9) p < 0.001, 6 months (RIC3-6) and 4 (RIC2-6) p ≤ 0.001 and 12 months 6 (RIC4-7) and 3 (RIC2-6) p < 0.001. Conclusions: There is an association between the malnutrition of the elderly with hip fracture and its mortality with a year of evaluation; we also find a difference in motor functionality.

¿Influye el consumo de comidas ricas en proteínas y grasas en la glucemia postprandial de pacientes con diabetes tipo 1 que realizan conteo de hidratos de carbono? / Does the consumption of meals rich in proteins and fats influence on the postprandial glucemia of patients with diabetes type 1 that follow carbohydrate counting?

Introducción: el tratamiento de la diabetes tipo 1 (DM1) requiere de la administración de insulina exógena; dentro de las variables a tener en cuenta para calcular la dosis se encuentra el contenido de hidratos de carbono (HC) de la comida a ingerir. Este macronutriente es considerado, desde hace varios años, el responsable del aumento de la glucemia postprandial (GPP). El conteo de hidratos de carbono (CHC) es el método más aceptado y utilizado actualmente en el tratamiento nutricional, aunque cada vez existe más evidencia de que hay otros macronutrientes, como las proteínas y las grasas, que pueden influir en la variación de la GPP. Objetivo: el objetivo de esta revisión bibliográfica es reunir los resultados de publicaciones científicas que analizaron la respuesta glucémica (RG) al consumo de comidas con alto contenido de proteínas y grasas y hacer un análisis de las diferentes intervenciones. Materiales y método: búsqueda bibliográfica en PUBMED, inicialmente 196 artículos. Luego de aplicar los criterios de inclusión y exclusión se seleccionaron 26 artículos realizados en personas con DM1 de los últimos 10 años (2007-2017) referidos al consumo de comidas altas en proteínas y grasas. Resultados: hay una significativa variación interpersonal en los requerimientos de insulina en respuesta a las grasas y proteínas dietarias, que puede fluctuar en un 65% ± 10%. En los estudios randomizados se logró determinar que en las comidas altas en grasas el pico de GPP fue demorado y la sensibilidad a la insulina fue menor. Uno de los estudios logró demostrar que el 100% de las comidas altas en grasa se asociaron con hiperglucemia tardía. En relación a las dos revisiones sistemáticas encontradas, se hace hincapié en la búsqueda de datos para mejorar el tratamiento intensificado de la DM1, siendo el control de la GPP el indicador principal, ponderando la importancia de considerar la ingesta proteica y grasa de manera adicional al CHC. Conclusión: se concluye que el efecto de una comida con un alto contenido en proteínas y grasas sobre la glucemia suele presentarse entre las 3 a 6 hs de consumidas, siempre teniendo en cuenta la respuesta individual y el modo de administrar la insulina. La tarea del equipo interdisciplinario es fundamental para conocer la respuesta individual en el paciente con DM1 ante el consumo de comidas altas en proteínas y grasas, pudiendo así orientar la toma de decisión(AU).

Introduction: the treatment of type 1 diabetes (DM1) requires the administration of exogenous insulin, being the carbohydrate (HC) content of the meal to be ingested one of the variables to be considered to calculate the insulin dose. For several years, this macronutrient has been considered responsible for the increase in postprandial glycemia (PPG). Carbohydrate Counting (CHC) is the most accepted and currently used method in the nutritional treatment, although there is enough evidence that other macronutrients, such as protein and fat, can influence on the variation of PPG. Objective: to gather the results of scientific publications which analysed the glycemic response (GR) to the consumption of high-protein and high-fat meals and to analyse de different interventions. After applying the inclusion and exclusion criteria, 24 articles were selected including those with individuals with DM1 from the past 10 years (with the exception of one) referring to the consumption of high-protein and high-fat meals. Results: there is a significant interpersonal variation in insulin requirements in response to dietary fat and protein, which can fluctuate by 65% +/- 10%. Randomized studies showed that in the high-fat meals, the peak of PPG was delayed and insulin sensitivity was lower. One of the studies showed that 100% of high-fat meals were associated with late hyperglycemia. Both systematic reviews emphasize the need to search for data to improve the intensive treatment of DM1, with the control of PPG being the main indicator, considering protein and fat intake, in addition to CHC. Conclusion: the effect on blood glucose of high-protein and high-fat meals usually occurs between 3 to 6 hours after being consumed, always considering the individual response and the insulin administration method. The task of the interdisciplinary team is essential to know the individual response in the DM1 patient to the consumption of high-protein and high-fat meals, thus being able to guide the decision-making process(AU).

Nevus epidérmicos y síndromes relacionados. Parte 1: nevus queratinocíticos / Epidermal Nevi and Related Syndromes - Part 1: Keratinocytic Nevi

Los nevus epidérmicos son hamartomas originados en la epidermis y/o en las estructuras anexiales de la piel que se han clasificado clásicamente partiendo de la morfología. En los últimos años se han descrito variantes nuevas y se han producido avances en el campo de la genética que han permitido caracterizar mejor estas lesiones y comprender su relación con algunas de las manifestaciones extracutáneas a las que se han asociado. En esta primera parte revisaremos los nevus derivados de la epidermis y los síndromes que se han descrito asociados a ellos

Epidermal nevi are hamartomatous lesions derived from the epidermis and/or adnexal structures of the skin; they have traditionally been classified according to their morphology. New variants have been described in recent years and advances in genetics have contributed to better characterization of these lesions and an improved understanding of their relationship with certain extracutaneous manifestations. In the first part of this review article, we will look at nevi derived specifically from the epidermis and associated syndromes

Nevus epidérmicos y síndromes relacionados. Parte 2: Nevus derivados de estructuras anexiales / Epidermal Nevi and Related Syndromes - Part 2: Nevi Derived from Adnexal Structures

Los nevus epidérmicos son hamartomas originados en la epidermis y/o en las estructuras anexiales de la piel que se han clasificado clásicamente partiendo de la morfología. En los últimos años se han descrito variantes nuevas y se han producido avances en el campo de la genética que han permitido caracterizar mejor estas lesiones y comprender su relación con algunas de las manifestaciones extracutáneas a las que se han asociado. En esta segunda parte revisaremos los nevus derivados de estructuras anexiales de la piel y los síndromes que se asocian

Epidermal nevi are hamartomatous lesions derived from the epidermis and/or adnexal structures of the skin; they have traditionally been classified according to their morphology. New variants have been described in recent years and advances in genetics have contributed to better characterization of these lesions and an improved understanding of their relationship with certain extracutaneous manifestations. In the second part of this review article, we will look at nevi derived from the adnexal structures of the skin and associated syndromes

Epidermal Nevi and Related Syndromes -- Part 1: Keratinocytic Nevi. / Nevus epidérmicos y síndromes relacionados. Parte 1: nevus queratinocíticos.

Epidermal nevi are hamartomatous lesions derived from the epidermis and/or adnexal structures of the skin; they have traditionally been classified according to their morphology. New variants have been described in recent years and advances in genetics have contributed to better characterization of these lesions and an improved understanding of their relationship with certain extracutaneous manifestations. In the first part of this review article, we will look at nevi derived specifically from the epidermis and associated syndromes.

Epidermal Nevi and Related Syndromes - Part 2: Nevi Derived from Adnexal Structures. / Nevus epidérmicos y síndromes relacionados. Parte 2: Nevus derivados de estructuras anexiales.

Epidermal nevi are hamartomatous lesions derived from the epidermis and/or adnexal structures of the skin; they have traditionally been classified according to their morphology. New variants have been described in recent years and advances in genetics have contributed to better characterization of these lesions and an improved understanding of their relationship with certain extracutaneous manifestations. In the second part of this review article, we will look at nevi derived from the adnexal structures of the skin and associated syndromes.

Carcinoma basocelular en pacientes jóvenes / Basal Cell Carcinoma in young adults

No disponible

Consumo de bebidas endulzadas artificialmente con edulcorantes no nutritivos y su relación con el desarrollo de síndrome metabólico y diabetes tipo 2 / Consumption of artificially sweetened beverages (BEA)with non-nutritive sweeteners and its relationship to the development of metabolic syndrome and type 2 diabetes

Introducción: En Argentina un 37,1% de la población padece sobrepeso, un 20,8% obesidad y un 9,8% diabetes. La prevalencia de síndrome metabólico oscila entre el 20 y 25%. Según el estudio HIDRATAR, el consumo promedio de agua, bebidas e infusiones era de 2.050 ml/día, de los cuales un 29% correspondió a bebidas endulzadas artificialmente (BEA). No existe consenso de los organismos internacionales para su consumo. Metodología: Se llevó a cabo una búsqueda bibliográfica en PubMed, Scielo y Cochrane, de artículos publicados a partir del año 2005, con el objetivo de conocer la relación entre el consumo de BEA y el riesgo de desarrollo de síndrome metabólico y diabetes mellitus tipo 2. Resultados: Se encontraron 12 trabajos que señalan los efectos adversos de las BEA. Los mismos representan una mayor población en estudio, seguida durante más tiempo. Es un tema controvertido con mucha disparidad en la obtención de la información, teniendo en cuenta además que, en el caso de estudios con humanos, son muchos los componentes del plan alimentario que hay que considerar. Conclusiones: Ha quedado demostrado que los edulcorantes no nutritivos no son sustancias metabólicamente inertes y hay evidencia que sugiere que las BEA no son completamente inocuas, siendo primordial y necesaria la educación para limitar su consumo y promover la ingesta de agua.

Adverse effects of tempol on hidrosaline balance in rats with acute sodium overload.

We studied the effects of tempol, an oxygen radical scavenger, on hydrosaline balance in rats with acute sodium overload. Male rats with free access to water were injected with isotonic (control group) or hypertonic saline solution (0.80 mol/l NaCl) either alone (Na group) or with tempol (Na-T group). Hydrosaline balance was determined during a 90 min experimental period. Protein expressions of aquaporin 1 (AQP1), aquaporin 2 (AQP2), angiotensin II (Ang II) and endothelial nitric oxide synthase (eNOS) were measured in renal tissue. Water intake, creatinine clearance, diuresis and natriuresis increased in the Na group. Under conditions of sodium overload, tempol increased plasma sodium and protein levels and increased diuresis, natriuresis and sodium excretion. Tempol also decreased water intake without affecting creatinine clearance. AQP1 and eNOS were increased and Ang II decreased in the renal cortex of the Na group, whereas AQP2 was increased in the renal medulla. Nonglycosylated AQP1 and eNOS were increased further in the renal cortex of the Na-T group, whereas AQP2 was decreased in the renal medulla and was localized mainly in the cell membrane. Moreover, p47-phox immunostaining was increased in the hypothalamus of Na group, and this increase was prevented by tempol. Our findings suggest that tempol causes hypernatremia after acute sodium overload by inhibiting the thirst mechanism and facilitating diuresis, despite increasing renal eNOS expression and natriuresis.

Role of angiotensin II and oxidative stress in renal inflammation by hypernatremia: benefits of atrial natriuretic peptide, losartan, and tempol.

The body regulates plasma sodium levels within a small physiologic range, despite large variations in daily sodium and water intake. It is known that sodium transport in the kidneys plays an important role in hypoxia, being the major determinant of renal oxygen consumption. Tubular epithelial cell hypoxia is an important contributor to the development of renal inflammation, and the damage may progress to structural injury, ending in acute renal failure. In this review, we will summarize the renal inflammatory effects of high acute plasma sodium (acute hypernatremia), and the molecular mechanisms involved. We will also discuss recent findings related to the role of oxidative stress and angiotensin II (Ang II) in the pathogenesis of renal injury. We will comment on the effects of agents used to prevent or attenuate the inflammatory response, such as the atrial natriuretic peptide, the superoxide dismutase mimetic - tempol, and losartan.

Signaling pathways involved in renal oxidative injury: role of the vasoactive peptides and the renal dopaminergic system.

The physiological hydroelectrolytic balance and the redox steady state in the kidney are accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Angiotensin II, atrial natriuretic peptide and intrarenal dopamine play a pivotal role in this interactive network. The balance between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide, by one side, and the prooxidant effect of the renin angiotensin system, by the other side, contributes to ensuring the normal function of the kidney. Different pathological scenarios, as nephrotic syndrome and hypertension, where renal sodium excretion is altered, are associated with an impaired interaction between two natriuretic systems as the renal dopaminergic system and atrial natriuretic peptide that may be involved in the pathogenesis of renal diseases. The aim of this review is to update and comment the most recent evidences about the intracellular pathways involved in the relationship between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide and the prooxidant effect of the renin angiotensin system in the pathogenesis of renal inflammation.

Acute sodium overload produces renal tubulointerstitial inflammation in normal rats.

The aim of the present study was to determine whether acute sodium overload could trigger an inflammatory reaction in the tubulointerstitial (TI) compartment in normal rats. Four groups of Sprague-Dawley rats received increasing NaCl concentrations by intravenous infusion. Control (C): Na+ 0.15 M; G1: Na+ 0.5 M; G2: Na+ 1.0 M; and G3: Na+ 1.5 M. Creatinine clearance, mean arterial pressure (MAP), renal blood flow (RBF), and sodium fractional excretion were determined. Transforming growth factor beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA), RANTES, transcription factor nuclear factor-kappa B (NF-kappaB), and angiotensin II (ANG II) were evaluated in kidneys by immunohistochemistry. Animals with NaCl overload showed normal glomerular function without MAP and RBF modifications and exhibited a concentration-dependent natriuretic response. Plasmatic sodium increased in G2 (P < 0.01) and G3 (P < 0.001). Light microscopy did not show renal morphological damage. Immunohistochemistry revealed an increased number of ANG II-positive tubular cells in G2 and G3, and positive immunostaining for NF-kappaB only in G3 (P < 0.01). Increased staining of alpha-SMA in the interstitium (P < 0.01), TGF-beta1 in tubular cells (P < 0.01), and a significant percentage (P < 0.01) of positive immunostaining for RANTES in tubular epithelium and in glomerular and peritubular endothelium were detected in G3 > G2 > C group. These results suggest that an acute sodium overload is able 'per se' to initiate TI endothelial inflammatory reaction (glomerular and peritubular) and incipient fibrosis in normal rats, independently of hemodynamic modifications. Furthermore, these findings are consistent with the possibility that activation of NF-kappaB and local ANG II may be involved in the pathway of this inflammatory process.

Impaired response to insulin associated with protein kinase C in chronic fructose-induced hypertension.

A fructose-enriched diet induces an increase in blood pressure associated with metabolic alterations in rats. Our hypothesis was that an increase in protein kinase C (PKC) activation, reported in the acute period of fructose overload, and an impaired vessel's response to vasoactive substances contribute to maintain elevated blood pressure levels in the chronic period. The aims of this study were to investigate in this animal model of hypertension: (1) if the increase in PKC activation was also found in the chronic stage; (2) the involvement of nitric oxide and insulin in the vessel's response; and plasma atrial natriuretic factor and nitrites/nitrates (nitric oxide metabolites) behavior. We evaluated the effects of: PKC-stimulator 12,13-phorbol dibutyrate, phenylephrine, insulin, nitric oxide synthase-inhibitor NG-nitro-L-arginine methyl esther (L-NAME) and PKC-inhibitor Calphostin C on aortic rings responses of Sprague-Dawley rats: fructose-fed and control. The fructose-fed group showed higher contractility to 12,13-phorbol dibutyrate than the control group in aortic rings pre-incubated with insulin, and this difference disappeared with L-NAME. The response to phenylephrine in rings pre-incubated with Calphostin C was decreased in the fructose-fed group and increased with Calphostin C plus L-NAME. Fructose-fed rats showed higher levels of plasma atrial natriuretic factor and nitrites/nitrates than controls. In conclusion, chronic fructose feeding seems to develop an impaired response to insulin, dependent on nitric oxide, suggesting a PKC alteration. Vasorelaxant agents, such as atrial natriuretic factor and nitric oxide, would behave as compensatory mechanisms in response to high blood pressure.

Serotonin hypersensitivity in aorta of two kidney-two clip hypertensive rats: calcium contribution and prostanoids-nitric oxide interactions.

Previous studies from our own laboratory have shown that abdominal aorta rings from two kidney - two clip hypertensive rats (HT) develop hypersensitivity to serotonin (SER) which is related to a decreased nitric oxide (NO) availability and enhanced thromboxane A2 production. In the present study we investigated whether calcium and prostanoid-NO interactions are involved in these findings. To this purpose, the aortic responses to SER were analyzed in calcium-free medium and in calcium-depleted aorta placed in normal medium. Moreover, effects of ridogrel (RID, an antagonist of TxA 2/PGH2 receptors and inhibitor of thromboxane synthetase) were analysed by cumulative dose-response curves to SER in the presence and in the absence of the NO synthase inhibitor N(omega)-nitro-L-arginine (NOLA). Vascular responses to SER in vessels from HT rats were associated with increased intracellular calcium mobilization. In addition, hypersensitivity to SER in HT group respect to sham group (SH) disappeared in the presence of RID, NOLA and RID plus NOLA. RID decreases the maximum tension to SER and this effect was prevented by NOLA. This inhibition was of a greater magnitude in rings from sham rats (SH): 34 +/- 6% than in HT rats: 15 +/- 6% (p < 0.05). Besides, RID decreased the sensibility to SER in the presence of NOLA only in the HT group. In conclusion, the present study suggests that SER hypersensitivity observed in HT rats is related to a facilitated intracellular calcium mobilization and enhanced TxA2-endoperoxide response. Changes in membrane SER-gated calcium channels opening are observed only during the early hypertensive period. Besides, the lower depressor effect of RID on the maximal tension to SER in aorta rings from HT rats are related with a decreased NO availability in this model of renovascular hypertension.

Effect of oral L-arginine administration for three weeks in two kidney-two clip hypertensive rats.

Nitric oxide (NO) has been identified as an effective vascular relaxant. This study analyses the contribution of the precursor L-arginine (L-arg) by oral administration in two kidney-two clip hypertension in the rat (2K-2C). Two groups were studied: sham (SH, n=21) and hypertensive (HT, n=15). After 4 weeks of surgery, a group of rats remained as controls (SHc and HTc, respectively), while others were supplemented with L-arg (1.25 g/L) in drinking water (SHa and HTa) for 3 weeks. Blood pressure was significantly increased in 2K-2C rats but remained unchanged after L-arg treatment. Plasma nitrite/nitrate concentrations were not different among groups. The contractile response of aorta to KCl, serotonin and the protein kinase C (PKC) stimulant, phorbol 12,13-dibutyrate (PDBu) was also evaluated. Higher contractile responses to PDBu (p<0.001) and lower relaxation to acetylcholine (Ach 10(-6) M, p<0.05 and 10(-5)M, p<0.02) were observed in aortic rings of HTc vs SHc; L-arg supplementation significantly diminished tension development to all agonists (p<0.05) but failed to modify the lower relaxation to Ach in HTa. Thromboxane (TxA(2)) - synthesis in rings of HTc was higher than in SHc under basal conditions (p<0.05). In the groups with supplement of L-arg, PDBu significantly stimulated prostacyclin (PGI(2)) synthesis more in HTa rats than in SHa ones (p<0.05). To conclude: 1) L-arg fails to modify hypertension development in 2K-2C rats; and 2) L-arg exerts a beneficial effect on the vascular wall, by reducing contractility in rings from HTa rats; it also improved PGI(2) synthesis under PDBu stimulation. 3) greater PKC activation and TxA(2) production rather than lower NO availability might result in systemic hypertension in 2K-2C rats.

Potential role of glycerol leading to rat fructose hypertension.

A fructose-enriched diet promotes hypertension in rats. We thought that an enhancement of the glycolytic and/or lipid disorder (s) that raise blood pressure could be the cause. Therefore, we studied 4 groups of Sprague-Dawley rats (+/-200 g): (1) control rats received a standard diet and tap water; (2) the glycerol group of rats received a standard diet and 0.54 mol/L glycerol in tap water; (3) the fructose group was given a fructose-enhanced diet (chow had 55% fructose instead of dextrin) and tap water; and (4) the fructose-glycerol group was given the fructose-enhanced diet and 0. 54 mol/L glycerol in drinking water. At the end of the second week, the findings were as follows. Blood pressure was 149+/-2 mm Hg in the fructose-glycerol group versus 129+/-2 (P<0.001), 131+/-2 (P<0. 001), and 140+/-3 (P<0.005) mm Hg in the control, glycerol, and fructose groups, respectively. Insulinemia was higher in the fructose-glycerol group than the control (P<0.001), glycerol (P<0. 001), and fructose groups (P<0.001); triglyceridemia was higher in the fructose-glycerol (P<0.02), fructose (P<0.05), and glycerol groups (P<0.02) than the control group. Thoracic aorta rings showed a lower ED(50) to 12,13-phorbol dibutyrate in the fructose-glycerol group than in the control (P<0.001), glycerol (P<0.002), and fructose groups (P<0.001). In conclusion, glycerol-fructose administration resulted in hypertriglyceridemia, hyperinsulinemia, and increased vascular sensitivity to 12,13-phorbol dibutyrate (with respect to the control group), and significantly greater expression of protein kinase C alpha and betaII (with respect to the glycerol group).

Atrial natriuretic factor in two kidney--two clip renovascular hypertension in the rat.

Hig levels of circulating atrial natriuretic factor (ANF) have been reported in several physiopathologic conditions like hypertension, heart and renal failure, pregnancy and high sodium intake. Nevertheless, neither relationships with water-sodium space regulation nor the role of an ANF vascular relaxant effect have been yet defined. The aim of present experiments was to characterize the contribution of circulating ANF and its vascular relaxing effects in the two kidney-two clip (2K2C) experimental model of renovascular hypertension. Complementary, plasma metabolites nitrite/nitrate of nitric oxide (NO) was examined because of mediation for both (NO an ANF) through cGMP. Three results showed (two-four weeks after surgery): indirect systolic blood pressure (mmHg), 186 +/- 4 in HT and 122 +/- 1 in SH (p < 0.001); a significant increase of plasma ANF (fmol/ml) in HT (n = 7, 1221 +/- 253) vs. SH (n = 9, 476 +/- 82; p < 0.02). Nitrate/nitrite plasma concentrations (mumol/l) were mpt different between SH and. The relaxant effect of ANF (10(-9), 10(-8) and 10(-7) M) on phenylephrine (3,5 x 10(-6) M) contracted rings from HT rats was smaller than SH rats (10(-8) M, p < 0.05). Contractions to phorbol 12, 13-dibutyrate (seven weeks after surgery) were significantly higher in rings from HT rats (p < 0.001). We conclude: 1) in addition to decreased granularity in atrial myocardiocytes, high circulating values of ANF here described suggest an increased turnover of the peptide in 2K2C hypertensive rats; 2) lower significant vascular relaxant effects in HT rats would indicate down regulation of ANF receptors in this model; the latter would derive from high plasma ANF concentration and, tentatively, because of greater activity of protein kinase C in the vascular wall; 39 similar values of plasma nitrite/nitrate in SH and HT rats would indicate a comparable NO circulating availability in both groups.

Nitric oxide and superoxide anions in vascular reactivity of renovascular hypertensive rats.

The present study intends to define the role of the endothelium derived relaxing factor nitric-oxide (EDRF-NO) and the reactive oxygen intermediates in hypersensitivity to 5-hydroxytryptamine (5-HT) observed in abdominal aorta rings of two kidney-two clip hypertensive rats. Methylene Blue (which blocks production of cGMP by EDRF-NO) and Nw-nitro-L-arginine (which inhibits EDRF-NO synthesis), both shifted 5-HT dose-response curves to the left and completely abolished the differences in sensitivity to the agonist. The aortic perfusion with Krebs-Alcohol 20% (v/v) suppressed vascular relaxation to Ach (10(-5) M) and also abolished differences in sensitivity to 5-HT. These results suggest that a lower availability of EDRF-NO accounts for a higher 5-HT sensitivity in vessels of hypertensive rats. On the contrary, ridogrel (inhibitor of tromboxane-synthase and blocker of PGH2 and TxA2 receptors) did not suppress the hypersensitivity to 5-HT. In addition, since the superoxide anion (O2-) inactivates EDRF-NO, the effects of Superoxide dismutase (SOD) and Catalase (CAT) added in the bath were analyzed. Significant changes in sensitivity (P < 0.005) were found only for vessels of hypertensive rats (SOD depressing and CAT increasing sensitivity to 5-HT). Complementary, SOD activity was evaluated in the aorta homogenates and was found to be significantly lower in the hypertensive rats [(differences between hypertensive and sham rats, mU.mg wet weight tissue-1: 7 days after clipping, -183 +/- 67 (n = 11), P < 0.02; 21 days, -160 +/- 70 (n = 9), p < 0.05]. Results would indicate: 1. Lower EDRF-NO availability in vessels of the hypertensive animals which would account for higher sensitivity to 5-HT; 2. Such a lower EDRF-NO might depend, in part, upon its greater inactivation by O2- anions; 3. A greater presence of O2- anions in the vessels of hipertensive rats that might be favored by the lower SOD activity concentration in the vascular wall.