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RESUMEN Se describe el caso de un varón de 68 años con antecedente de hipertensión arterial no tratada, diagnosticada un año antes, que ingresó con un cuadro de anasarca, debilidad muscular y disnea al reposo. Los primeros exámenes realizados mostraron hipopotasemia severa, alcalosis metabólica, litiasis renal y vesical y enfermedad renal crónica. La tomografía abdominal reveló una tumoración suprarrenal derecha, hidronefrosis bilateral y litiasis renal y vesical. Con la sospecha de hiperaldosteronismo primario se completó el estudio, con la determinación de relación aldosterona/concentración de renina directa, que resultó alta. El estudio metabólico arrojó hipercalciuria e hiperuricosuria y la gradiente transtubular de potasio mayor de 7. El paciente fue sometido a tratamiento quirúrgico con nefrectomía derecha, sin embargo, falleció en el postoperatorio inmediato, por shock hipovolémico e insuficiencia respiratoria. SUMMARY We report the case of a 68-year-old male with a history of non-treated arterial hypertension diagnosed the previous year that was admitted with anasarca, muscle weakness and dyspnea at rest. The first laboratory exams showed severe hypopotassemia, metabolic alkalosis, renal and gallbladder lithiasis and chronic renal disease. The abdominal tomography revealed a right suprarenal tumor, bilateral hydronephrosis and renal and gallbladder lithiasis. Under the suspicion of primary hyperaldosteronism, the diagnosis was confirmed with the determination of the relationship between aldosterone/direct renin concentration, which was high. The metabolic study showed hypercalciuria and hyperuricosuria and the potassium trans tubular gradient was above 7. The patient underwent right nephrectomy, nonetheless, died at the immediate post-operatory period due to a hypovolemic shock and respiratory failure.

RESUMEN La hipertensión arterial es una afección pandémica responsable de varias complicaciones cardiovasculares, neurológicas y renales. La gran mayoría se debe a la hipertensión esencial o primaria, pero cada vez se diagnostican más casos de hipertensión arterial secundaria, ya sea de causa endocrinológica, renal o neurológica. Se presenta un caso de hipertensión secundaria a hiperaldosteronismo primario. ABSTRACT Hypertension is a pandemic worldwide, being responsible for several cardiovascular, neurological and renal complications. The vast majority is due to essential or primary hypertension, but more and more cases of secondary arterial hypertension are diagnosed, either due to endocrinological, renal or neurological causes. Next, an hypertension case of secondary to primary hyperaldosteronism is presented.

The renin-angiotensin-aldosterone system modulates volume, sodium and potassium homeostasis. In the setting of a high sodium diet, up to 30% of patients with hypertension have a low or suppressed renin and increased volume. This phenotype of low renin hypertension (LRH) is multifactorial and includes infrequent inherited genetic syndromes, milder phenotypes of classic diseases and environmental exposures. All these conditions have in common a higher cardiovascular risk mediated by the over activation of the mineralocorticoid receptor (MR), present not only in the kidney, but also in vasculature, myocardium and adipocytes. Consequently, the aim of LRH treatment goes beyond the control of blood pressure and requires antagonizing MR with specific pharmacologic agents, pursuing normalization of renin as a clinical objective. Due to the unusual evaluation of renin status by non-endocrinologists and lack of disease awareness, only a minority of hypertensive patients receive this pathophysiologically-driven treatment that should reduce cardiovascular outcomes.

Introduction: Secondary hypertension corresponds to 15 % of the causes of arterial hypertension, and among them, primary hyperaldosteronism presents a variable incidence of about 3% in hypertensive patients. It has a slightly higher prevalence in women, between 30 and 60 years, and is usually unilateral. Case presentation: The authors describe the clinical case of a patient, followed by severe hypertension medicated with four antihypertensive drugs for tension stabilization, maintaining systolic arterial tensions superior to 170 mmHg. In the aetiological study of hypertension, analytical alterations suggested hyperaldosteronism and a nodular lesion was detected in the left adrenal gland. The patient was submitted to surgery and excision of the lesion was done with histological confirmation of the diagnosis of corticomedullary adenoma of the adrenal gland. The patient presented improvement of the tension profile, with the need to suspend two of the four antihypertensive drugs and to reduce the dose of the remaining ones. Conclusion: A tumor of the adrenal cortex producing aldosterone is the main cause of primary hyperaldosteronism and should always be excluded when the presence of di cult to control, severe hypertension is detected, since the standard treatment is surgical, leading to a stabilization of the tension pattern after a few months. Introducción: la hipertensión secundaria corresponde al 15% de las causas de hipertensión arterial, y entre ellas, el hiperaldosteronismo primario presenta una incidencia variable de sobre 3 % en pacientes hipertensos. Tiene una prevalencia ligeramente mayor en mujeres, entre 30 y 60 años, y generalmente es unilateral. Presentación de caso: los autores describen el caso clínico de un paciente, seguido por una hipertensión resistente medicada con cuatro fármacos antihipertensivos para la estabilización de la tensión, con mantenimiento de las tensiones arteriales sistólicas superiores a 170 mmHg. Las alteraciones analíticas en el estudio etiológico de la hipertensión sugirieron hiperaldosteronismo y una lesión nodular en la glándula suprarrenal izquierda. El paciente fue sometido a cirugía y se realizó la escisión de la lesión con confirmación histológica del diagnóstico de adenoma corticomedular de la glándula suprarrenal. El paciente presentó una mejora en el perfil de tensión, con la necesidad de suspender dos de los cuatro fármacos antihipertensivos y reducir la dosis de los restantes. Discusión: un tumor de la corteza suprarrenal que produce la aldosterona es la principal causa de hiperaldosteronismo primario y siempre debe excluirse cuando se presenta hipertensión grave, difícil de controlar, ya que el tratamiento estándar es quirúrgico y conduce a una estabilización del patrón de tensión después de unos meses. Introdução: a hipertensão secundária corresponde ao 15% das causas de hipertensão arterial, e entre elas, o hiperaldosteronismo primário apresenta uma incidência variável de sobre 3% em pacientes hipertensos. Tem uma prevalência ligeiramente maior em mulheres, entre 30-60 anos, e geralmente é unilateral. Apresentação do caso: os autores descrevem o caso clínico de um paciente, seguido por uma hipertensão resistente medicada com quatro fármacos anti-hipertensivos para a estabilização da tensão, com manutenção das tensões arteriais sistólicas a 170 mmHg. As alterações analíticas no estudo etiológico da hipertensão sugeriram hiperaldosteronismo e uma lesão nodular na glândula suprarrenal esquerda. O paciente foi submetido a cirurgia e se realizou a incisão da lesão com confirmação histológica do diagnóstico de adenoma córtico-medular da glândula suprarrenal. O paciente apresentou uma melhora no per l de tensão, com a necessidade de suspender dois dos quatro fármacos anti-hipertensivos e reduzir a dose dos restantes. Discussão: um tumor do córtex suprarrenal que produz a aldosterona é a principal causa de hiperaldosteronismo primário e sempre deve excluir-se quando se apresenta hipertensão grave, difícil de controlar, pois o tratamento standard é cirúrgico e conduz a uma estabilização do patrão de tensão depois de uns meses.

Introduction: Over the past decade, obesity has become a risk factor for developing chronic kidney disease. Proteinuria is known to be an independent determinant of the progression of chronic kidney disease, and adipose tissue is a recognized source of components of the renin–angiotensin–aldosterone system (RAAS). Recent studies have shown that plasma aldosterone levels are disproportionately higher in patients with obesity. Drugs that block the RAAS are unable to inhibit aldosterone in the long term. The aim of our study was to analyze the renoprotective effect of an aldosterone antagonist in combination with RAAS blockers in patients with obesity and proteinuric nephropathy. Material and methods: This study is a substudy of previously published study on the renoprotective effect of mineralocorticoid receptor blockers in patients with proteinuric nephropathies. Patients with proteinuria levels >1 g/24 h who were taking spironolactone and were being treated with other RAAS blockers were divided according to body mass index (BMI) into an obesity group (BMI ≥30 kg/m2) and a control group. Results: Seventy-one patients were included in the study, with a mean age of 56.7 ± 15.1 years. More than 50% of the patients in both groups had diabetes. Thirty-two patients were included in the obesity group and 39 were included in the control group. There were no significant differences in renal function, proteinuria, blood pressure, serum potassium levels and the percentage of RAAS blockers in both groups. After a follow-up of 28.9 (14–84) months, there was a 59.4% reduction in proteinuria in the obesity group (2.8 ± 2.1 vs. 1.3 ± 1.6 g/24 h, p

Resumen: La hiperplasia suprarrenal congénita debida al déficit de 21-hidroxilasa es una enfermedad autosómica recesiva causada por mutaciones en el gen CYP21A2. En las formas clásicas se produce defecto de cortisol y aldosterona (insuficiencia suprarrenal y pérdida salina) y virilizacion de la recién nacida afecta con ambigüedad genital. En este artículo ofrecemos algunas recomendaciones para el diagnóstico, que debe ser lo más precoz posible, y el tratamiento, adecuado e individualizado. El estudio genético del paciente y su familia es clave en el diagnóstico del propio afectado, y también permite establecer el consejo genético, así como el diagnóstico y tratamiento prenatales en futuros embarazos. Abstract: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations in the CYP21A2 gene. Cortisol and aldosterone synthesis are impaired in the classic forms (adrenal insufficiency and salt-wasting crisis). Females affected are virilised at birth, and are at risk for genital ambiguity. In this article we give recommendations for an early as possible diagnosis and an appropriate and individualised treatment. A patient and family genetic study is essential for the diagnosis of the patient, and allows genetic counselling, as well as a prenatal diagnosis and treatment for future pregnancy.

Este artículo se encuentra disponible en la siguiente URL: https://cjas.agriculturejournals.cz/pdfs/cjs/2017/06/05.pdf Many physiological events occurring during the estrous cycle, including folliculogenesis, oocyte maturation, ovulation, follicular atresia, corpus luteum development, luteolysis, steroidogenesis, and angiogenesis are associated with an increased expression of the renin–angiotensin–aldosterone system (RAAS) in uterus and ovarian follicles. This enhanced expression leads to a rise in plasma concentrations of these hormones in women and laboratory animals, and the same might happen in the mare. This study aims to assess if an activation of the RAAS occurs in mares around ovulation and if this activation is related to the diameter of the predominant follicle (DPF), packed cell volume (PCV), and electrolyte concentrations. Twenty-five healthy Spanish Purebred mares were sampled during the five days before ovulation, the day of ovulation, and the first five days after ovulation. Renin (REN) concentrations increased progressively during the five days before ovulation, achieving the highest values on the day of ovulation. Angiotensin (ANG) concentrations showed a sharp decrease after ovulation, with the lowest values the fifth day after it. Aldosterone (ALD) concentrations increased progressively, from the fifth day before ovulation until the fifth day after ovulation. The highest PCV values were found on the day of ovulation. There were no relevant correlations between the RAAS components and electrolytes concentrations. Before ovulation, there was a positive relationship between REN and ALD (r = 0.760) and after ovulation, a negative correlation between ANG and ALD (r = –0.660). The DPF was correlated with REN (r = 0.740) and with ALD (r = 0.800) concentrations. Ovulation in the mare is associated with high plasma REN concentrations, and therefore, with an activation of the RAAS. In addition, after ovulation, the sharp decrease in plasma REN and ANG concentrations might be a reflex of the modulation of the previously activated RAAS, although plasma ALD concentrations increased during this period.

El Hiperparatiroidismo primario (HPTP) es un trastorno endocrino frecuente caracterizado por una secreción autónoma de hormona paratiroidea (PTH). Si bien, su variante asintomática es la más frecuentemente encontrada en la práctica clínica (la cual se diagnostica incidentalmente), las complicaciones óseas y renales afectan de forma importante la calidad de vida del paciente. Sin embargo, el espectro de manifestaciones de este trastorno no se limita al metabolismo mineral, puesto que las concentraciones elevadas de PTH se asocian a un mayor riesgo de alteraciones metabólicas como el síndrome metabólico, diabetes mellitus 2 y enfermedades cardiovasculares. En este ámbito, la hipertensión arterial (HTA), relacionada con aproximadamente 9,4 millones de muerte al año, ha sido considerada una manifestación no clásica del HPTP. La interacción PTH-Aldosterona ha surgido como un importante eslabón para tratar de explicar esta relación, planteándose diversos mecanismos teóricos que posicionan a la PTH como estimulador directo de la síntesis de aldosterona en las células de la zona glomerular. Sin embargo, estos mecanismos teóricos han estado rodeados de controversia en su aspecto epidemiológico y clínico, existiendo aún muy pocos estudios poblacionales explorando este vínculo y su relación con la morbimortalidad cardiovascular, por lo que es necesario mayor investigación en el área con el fin de conocer el verdadero impacto de estos mecanismos en la salud de los individuos. Esta revisión resume aspectos del metabolismo del calcio, al igual que los principales mecanismos subyacentes al vínculo HPTP-HTA, y los datos epidemiológicos disponibles sobre el tópico, a fin de brindar un mejor entendimiento sobre este novel planteamiento. Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by autonomic parathyroid hormone secretion (PTH). Although its asymptomatic variant is the most frequently found in clinical practice (which is incidentally diagnosed), bone and kidney complications significantly affect the patient’s quality of life. However, the spectrum of manifestations of this disorder is not limited to mineral metabolism, since elevated concentrations of PTH are associated with an increased risk of metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease. In this area, hypertension (AHT), related to approximately 9.4 million deaths per year, has been considered a non-classical manifestation of PHPT. The interaction PTH-Aldosterone has emerged as an important link to try to explain this relationship, posing various theoretical mechanisms that position PTH as a direct stimulator of aldosterone synthesis in the glomerular zone cells. However, these theoretical mechanisms have been surrounded by controversy in their epidemiological and clinical aspects, and there are still very few population studies exploring this link and its relation with cardiovascular morbimortality, which is why more research is needed in the area in order to know. The true impact of these mechanisms on the health of individuals. This review summarizes aspects of calcium metabolism, as well as the main mechanisms underlying the HPTP-HTA link, and available epidemiological data on the topic, in order to provide a better understanding of this novel approach.

Previamente hemos demostrado que la eficacia de enalapril, candesartán y de fasudil -inhibidor de la vía RhoA/ROCK,- en el tratamiento del remodelado cardíaco en la hipertensión (HTA) e infarto al miocardio está mediada por aumento en los niveles circulantes del péptido vasoactivo angiotensina [Ang]-(1-9). Sin embargo, no hay información disponible si el antagonista del receptor de mineralocorticoide, espironolactona (espiro) disminuye el remodelado cardíaco aumentando los niveles circulantes de Ang-(1-9). El objetivo de este trabajo fue determinar si espironolac-tona disminuye el remodelado cardíaco aumentando los niveles circulantes de Ang-(1-9) en la hipertensión arterial experimental. Métodos. Estudio comparativo de 3 grupos experimentales. Se utilizaron ratas Sprague Dawley macho (150 ± 10 grs) unifrectomizadas tratadas con desoxi-corticosterona (DOCA, 60mg/Kg 2 veces sem, im) por 6 semanas. Como controles (Sham) se usaron ratas unifrectomizadas. A partir de la 3° semana las ratas DOCA con HTA> 140 mmHg fueron randomizadas a recibir vehículo o espiro (100 mg/kg día, gavage) por 3 sem. Al finalizar el tratamiento se determinó la presión arterial sistólica (PAS), masa corporal, peso del corazón (PC) y masa cardíaca relativa al largo de la tibia (MCR, mg ventrículos/LT*100). El grado de hipertrofia car-diomiocitaria se determinó midiendo el área y perímetro de los cardiomiocitos y la fibrosis por el contenido de colágeno en cortes teñidos con rojo picrosirio. Resultados (promedio ± ES): Conclusión: Espironolactona disminuye la PAS y aumenta los niveles circulantes de Ang-(1-9). Este aumento en los niveles circulantes de Ang-(1-9) se asocia con una disminución significativa de la hipertrofia y la fibrosis cardiaca hipertensiva. Este nuevo efecto de espironolactona en los niveles circulantes de Ang-(1-9), - péptido vasoactivo de la vía paralela del sistema renina-angiotensina-aldosterona,- podría contribuir al efecto antihipertensivo y disminución del daño cardiaco en la hipertensión y remodelamiento cardiovascular y renal patológico. Estos hallazgos pueden tener relevancia terapéutica en términos que Ang-(1-9) podría disminuir el daño cardiovascular patológico. We have previously demonstrated that the efficacy of enalapril, candesartan and fasudil,- RhoA / ROCK inhibitor-, in the treatment of cardiac remodeling in hypertension (HT) and myocardial infarction is mediated by an increase in circulating levels of the vasoactive peptide angiotensin (Ang) -(1-9). However, it is not known whether the mineralocorticoid receptor antagonist, spironolactone (spiro) decreases cardiac remodeling by increasing the circulating levels of Ang- (1-9). The aim of this study was to determine whether spironolactone decreases cardiac remodeling by increasing circulating levels of Ang-(1-9) in experimental hypertension. Methods. Comparative study of 3 experimental groups. Unifirectomized male Sprague Dawley rats (150 ± 10 grams) were treated with deoxycorticos-terone (DOCA, 60 mg / kg 2 times a week, im) for 6 weeks. Unifirectomized rats were used as controls (Sham). At 3rd week after surgery, DOCA rats with HTA> 140 mmHg were randomized to receive vehicle or spironolactone (Spiro, 100 mg / kg day, gavage) for 3 weeks. At the end of treatment, systolic blood pressure (SBP), body mass (BM), heart weight (HW) and relative cardiac mass to the tibia length (MCR, mg ventricles / LT * 100) were determined. The degree of cardiomyocyte hypertrophy was determined by measuring the area and perimeter of cardiomyocytes and fibrosis by collagen content in sections stained with picrosirius red. Results (mean ± ES): Conclusion: Spironolactone decreases systolic blood pressure and increases circulating levels of Ang-(1-9). This increase in circulating levels of Ang- (1-9) was associated with a significant decrease in hypertrophy and hypertensive cardiac fibrosis. This new effect of spironolactone on the circulating levels of Ang- (1-9) - vasoactive peptide of the parallel pathway of the re-nin-angiotensin-aldosterone system - could contribute to the antihypertensive effect and decrease of cardiac damage in HT and cardiovascular remodeling and renal disease. These findings may have therapeutic relevance supporting that Ang-(1-9) may decreases pathologic cardiovascular damage.

Previamente hemos demostrado que la eficacia de enalapril, candesartán y de fasudil -inhibidor de la vía RhoA/ROCK,- en el tratamiento del remodelado cardíaco en la hipertensión (HTA) e infarto al miocardio está mediada por aumento en los niveles circulantes del péptido vasoactivo angiotensina [Ang]-(1-9). Sin embargo, no hay información disponible si el antagonista del receptor de mineralocorticoide, espironolactona (espiro) disminuye el remodelado cardíaco aumentando los niveles circulantes de Ang-(1-9). El objetivo de este trabajo fue determinar si espironolac-tona disminuye el remodelado cardíaco aumentando los niveles circulantes de Ang-(1-9) en la hipertensión arterial experimental. Métodos. Estudio comparativo de 3 grupos experimentales. Se utilizaron ratas Sprague Dawley macho (150 ± 10 grs) unifrectomizadas tratadas con desoxi-corticosterona (DOCA, 60mg/Kg 2 veces sem, im) por 6 semanas. Como controles (Sham) se usaron ratas unifrectomizadas. A partir de la 3° semana las ratas DOCA con HTA> 140 mmHg fueron randomizadas a recibir vehículo o espiro (100 mg/kg día, gavage) por 3 sem. Al finalizar el tratamiento se determinó la presión arterial sistólica (PAS), masa corporal, peso del corazón (PC) y masa cardíaca relativa al largo de la tibia (MCR, mg ventrículos/LT*100). El grado de hipertrofia car-diomiocitaria se determinó midiendo el área y perímetro de los cardiomiocitos y la fibrosis por el contenido de colágeno en cortes teñidos con rojo picrosirio. Resultados (promedio ± ES): Conclusión: Espironolactona disminuye la PAS y aumenta los niveles circulantes de Ang-(1-9). Este aumento en los niveles circulantes de Ang-(1-9) se asocia con una disminución significativa de la hipertrofia y la fibrosis cardiaca hipertensiva. Este nuevo efecto de espironolactona en los niveles circulantes de Ang-(1-9), - péptido vasoactivo de la vía paralela del sistema renina-angiotensina-aldosterona,- podría contribuir al efecto antihipertensivo y disminución del daño cardiaco en la hipertensión y remodelamiento cardiovascular y renal patológico. Estos hallazgos pueden tener relevancia terapéutica en términos que Ang-(1-9) podría disminuir el daño cardiovascular patológico.

Introducción. El estado hídrico previo al inicio de un ejercicio (hiperhidratación-deshidratación o hipohidratación y euhidratación) modifica la respuesta neurohumoral.En personas, la deshidratación origina una liberación incrementada de las hormonasimplicadas en el mantenimiento de la volemia y del estado hidroelectrolítico, tales comola renina (REN), angiotensina (ANG) y aldosterona (ALD). La testosterona (T) es unahormona anabólica, mientras que el cortisol (C) es una hormona de estrés, con funcionescatabólicas. El cociente T/C es un reflejo de la intensidad anabólica/catabólica de unejercicio y en atletas humanos, se ve afectada por el estado hídrico.Objetivos. 1) Describir las variaciones en las concentraciones de REN, ANG, ALD, T, Cy ratio T/C en caballos durante un ejercicio de tiro y arrastre, en relación con otrosmarcadores de equilibrio hidroelectrolítico y en función de la carga arrastrada; 2)Analizar si la respuesta de estas hormonas al ejercicio difiere entre animales condeshidratación hipertónica y euhidratados;Hipótesis: 1) Que las concentraciones de REN, ANG, ALD, T, C serán más elevadas enlos caballos deshidratados que en los euhidratados; 2) Que el ejercicio de tiro y arrastre,particularmente en los animales de mayor peso corporal, inducirá una mayor activacióndel eje REN, ANG, ALD y una liberación superior de T; 3) Que los animalesdeshidratados experimentarán un incremento más intenso de estas hormonas en respuestaal ejercicio.Material y métodos. Se han llevado a cabo dos estudios simultáneos. En el estudio I, sehan analizado los siguientes parámetros: valor hematócrito (HTO), albúmina (ALB),sodio (Na), potasio (K), cloro (Cl), lactato (LA) y concentraciones séricas de REN, ANGy ALD y en el estudio II, se han determinado las concentraciones de ALB, T, C y ratioT/C. En el estudio I, se han incluido 64 caballos machos, enteros y castrados, divididos en dos grupos según su estado hídrico: grupo control o euhidratado (CTR, n=11) y grupodeshidratado (DH; n=53), con deshidratación hipertónica inducida por restricción de aguay comida. Además, según su peso corporal, los animales se han dividido en 3 categoríasde peso: I (451 kg; n=5 para CTR; n=12 para DH). En el estudio II, sehan incluido los mismos animales, con excepción de la categoría de peso III para el grupoCTR, que solo está constituida por 3 animales, en lugar de 5, al descartar a los machoscastrados, debido a la medición de T. Todos los animales, realizaron un ejercicioconsistente en recorrer una pista de arena de playa de 60 m de longitud, tirando de uncarruaje, con 2, 2,25 y 2,5 veces su peso corporal para las tres categorías de peso. La pistade arena se dividió en cuatro áreas de 15 m, en cada una de las cuales, el animal hizo unaparada obligatoria, de duración decidida por el acompañante, y que se incluyó comotiempo de carrera. Los animales eran eliminados si se superan los 5 min de duración. Enlos dos estudios, se tomaron muestras de sangre en los siguientes tiempos: en reposo,antes del ejercicio (R), dentro del primer minuto tras finalizar el ejercicio (E) y a los 5,10, 15 y 30 minutos de una recuperación pasiva (5REC, 10REC, 15REC y 30REC).Resultados. Estudio I. La diferencia de peso de los caballos tuvo una influencia mínimaen los valores basales y en la respuesta al ejercicio. En reposo, los caballos DH tuvieronvalores superiores de HTO, ALB, LA, Na, K y ANG en comparación con los CTR. Elejercicio condicionó una elevación de HTO, ALB, LA y Na, tanto en los caballos CTRcomo en los DH. Se encontró un incremento de ANG en los caballos DH y de ALD enlos caballos CTR. La elevación con el ejercicio experimentada por los parámetrosanalizados fue de magnitud similar en los grupos CTR y DH, con excepción del LA(incrementó más en DH) y ALD (aumentó más en CTR). Estudio II. El ejercicio dio lugara un aumento de T en las categorías I y III de los grupos CTR y DH, así como undescenso en la categoría II del grupo CTR. El C mostró un aumento progresivo en las trescategorías y en los dos grupos de estado hídrico, con los valores máximos en el tiempo30REC. El ratio T/C aumentó en la categoría III del grupo DH, descendió en la categoríaII del grupo CTR y no varió en los otros casos. Los animales DH, independientemente dela categoría de peso, tuvieron valores superiores de T y C, en la mayoría de los tiempos de extracción de muestras. Sin embargo, si se consideran los cambios experimentados porestas hormonas durante el ejercicio o en la recuperación, en relación a los valores basales,el aumento del C fue más marcado en el grupo CTR que en el DH, para las tres categoríasde peso. Las variaciones de la concentración de T fueron superiores en las categorías depeso I y III del grupo CTR que en el grupo DH. El ratio T/C fue estadísticamente igualentre caballos CTR y DH en las categorías I y III, mientras que en la categoría II, loscaballos DH presentaron cocientes T/C mayores.Conclusiones. La deshidratación hipertónica altera la concentración de las hormonasimplicadas en la regulación del equilibrio hidro-electrolítico, de la presión sanguínea ydel metabolismo. Sin embargo, el estado hídrico previo al ejercicio tiene una acciónmínima sobre la magnitud de estos cambios en respuesta a un ejercicio de tiro y arrastrede corta duración (inferior a 5 min).Relevancia. Se ha demostrado que la respuesta neurohumoral, determinada en base a lasconcentraciones circulantes de las hormonas REN, ANG, ALD, T y C, se ve afectada porel ejercicio cuando el animal empieza el mismo en estado de euhidratación o dedeshidratación., Introduction. Hydration status prior to exercise (hyperhydration-dehydration orhypohydration) modifies neurohumoral response to subsequent exercise. In humanbeings, dehydration elicits an increased release of hormones involved in the maintenanceof volemia and hydric and electrolyte balance, such as renin (REN), angiotensin II (ANG)and aldosterone (ALD). Cortisol (C) is a stress hormone with catabolic functions,whereas testosterone (T) has anabolic actions. Therefore, T/C ratio reflexesanabolic/catabolic balance during or after an exercise and in humans, it changesaccording to hydration.Objectives: 1) To describe changes in REN, ANG, ALD, T and C concentrations andT/C ratio in horses during a pulling exercise, in relation to other biomarkers of hydrationand the load pulled; 2) To analyze whether the response of these hormones is differentbetween euhydrated animals compared to those with hypertonic dehydration.Hypothesis. 1) REN, ANG, ALD, T and C concentrations would be higher in dehydratedthan in euhydrated horses; 2) Pulling exercise in horses, particularly in the heaviestanimals, would lead to a greater activation of the REN, ANG and ALD axis and a greaterrelease of T; 3) Dehydrated animals would show a greater increase of circulatingconcentrations of these hormones in response to exercise.Material and methods. Two simultaneous studies have been performed. In the study I,the following parameters have been measured: packed cell volume (PCV), albumin(ALB), sodium (Na), potassium (K), chloride (Cl), lactate (LA), REN, ANG and ALD. Inthe study II, the concentrations of ALB, T and C were measured and the ratio T/C wascalculated. Sixty-four male (both intact and castrated) were included in the study I,divided into two groups according to their hydration previously to the exercise: controlgroup or euhydrated (CTR; n=11) and dehydrated group (DH; n=53), with hypertonic dehydrated induced by water and food restriction. In addition, according to their bodyweight, horses were divided into three body weight categories: I (451 kg; n=5 forCTR; n=12 for DH). The same animals were included in the study II, with the exceptionof two animals of the category III of group CTR, which were excluded because they weregeldings. All the animals carried out an exercise consisting in covering a sand beach track60 m long, pulling a carriage loaded with 2, 2.25 or 2.5 times their body weight, for thethree categories respectively. The track was divided into three sections of 20 m each,where the animals have compulsory stop. The duration of the stop is selected by theaccompanier person, but it is included in the time of exercise and the animal is eliminatedfrom competition if a total duration of 5 min is exceeded. In both studies, blood samples were taken at rest, before exercise (R), within the first minute after exercise (E), and at 5,10, 15 and 30 min of a passive recovery (5REC, 10REC, 15REC and 30REC).Results. Study I. The different body weight of the horse has a minor influence on theresting values and in the response to exercise. In resting conditions, DH horses exhibitedhigher PCV, ALB, LA, Na, K, Cl and ANG-II levels compared to CTH horses. Exerciseled to an increase in PCV, ALB, LA and Na, both in CTR and DH groups. An increase inANG in DH horses and ALD in CTR horses was found in response to exercise. The risewith the exercise presented by the studied parameters was of similar magnitude in thegroups CTR and DH, with the exception of LA (greater increase in DH) and ALD(greater increase in CTR). Study II. C concentrations presented a progressive increase inthe three body weight categories and in the two groups of horses with different hydration,achieving the highest values at time 30REC. Serum T concentrations rose with exercisein categories I and III of group CTR and DH, but experienced a reduction in category IIof group CTR. T/C ratio increased in category III of group DH, decreased in category IIof group CTR and it did not change in the other cases. DH horses, nevertheless of bodyweight category and in most of the sampling times, had higher T and C values. However,if we consider the changes underwent by these hormones during exercise or recuperationcompared to resting values, the increase of C concentrations was more marked in thegroup CTR than in the group DH, for the three body weight categories. The variations in serum T concentrations were more marked in categories I and III of group CTR than ingroup DH. Significant differences in the T/C ratio between CTR and DH in categories Iand III were not found, whereas horses DH of category II had higher T/C ratios.Conclusions. The hypertonic dehydration alters the circulating concentrations of thehormones implied in the regulation of hydration, electrolyte balance, blood pressure andmetabolism. However, hydration status prior to the exercise exerts a minor effect on themagnitude of these changes in response to a pulling exercise of short duration (shorterthan 5 min).Relevance. It has been demonstrated that the neurohumoral response to exercise,determined in based of the circulating concentrations of REN, ANG, ALD, T and Cdiffers when the horse begins the exercise with euhydration or dehydration.

One of the particularities that develops the cardiorenal syndrome (CRS) is a circle in which as a consequence of the low cardiac output there is an alteration in the balance of nitric oxide and in the release of antidiuretic hormone, among others; induction of renal vasoconstriction and increased reabsorption in the proximal tubule of water and sodium reduces the supply of water and sodium at the level of the distal tubule, which causes a decrease in the diuresis of the natriuretic peptide and increases sensitivity to the action of aldosterone (secreted by the adrenal glands) which acts in the conservation of sodium and secreting potassium and increasing blood pressure). This explains that in patients with cardiac insufficiency (CI), one of the most evident characteristics is hypervolemia and sodium retention. Recent data support that, in CRS, fluid and sodium retention and subsequent resistance to diuretics cause progressive volume overload and worsening of HF, with reduced cardiac output and increased renal dysfunction. Consequently, a situation with a poor prognosis and few alternative options is generated.

La privación dietaria de sodio estimula la secreción de aldosterona. En el colon de rata, la aldosterona elevada aumenta la absorción de Na+, pero además torna electrogénico el mecanismo de absorción (normalmente electroneutro). Dicho transporte electrogénico puede suprimirse mediante el bloqueo de los canales epiteliales de Na+ en la membrana apical o la inhibición de la Na, KATPasa de la membrana basolateral. La absorción electrogénica de sodio está estrechamente acoplada al metabolismo aerobio, pero se desconoce si el bloqueo de los canales de Na+ reduce el consumo de oxígeno en igual medida que la inhibición de la Na, K-ATPasa. Se obtuvieron preparados de mucosa aislada del colon distal de ratas alimentadas con una dieta hiposódica por 10 días. Se determinó simultáneamente la corriente de cortocircuito y el consumo de oxígeno en condición basal y luego del bloqueo de canales de Na+ con amilorida (n=12) o de la Na, K-ATPasa con uabaína (n=12). Ambos tratamientos redujeron la corriente de cortocircuito en igual medida (>80%), pero la reducción en el consumo de oxígeno fue mayor con uabaína que con amilorida (p

La hipertensión arterial secundaria es más común en individuos menores de 30 años, la mayor parte son de causa renovascular; la etiología endocrina es excepcional, el hiperaldosteronismo primariosólo ocupa de 5-15%, el síndrome de Conn corresponde a 0.05-2.2% de la población de hipertensos y es una de las pocas causas potencialmente curables de hipertensión, por lo que consideramos este caso digno de ser revisado. Se presenta un hombre de 63 años de edad con hipertensión arterialdiagnosticada hace 25 años, en tratamiento con múltiples antihipertensivos, incluido el minoxidil sin control de cifras tensionales, que consulta a endocrinología por aparición de vello facial. Se consideró hipertensión arterial secundaria y se halló hipokalemia. La relación de aldosterona y renina elevada, sugería la presencia de hiperaldosteronismo, que se localizó con venografía de suprarrenales. La extirpación quirúrgica de la lesión confirmó el diagnóstico de adenoma adrenocortical. Después de la cirugía mejoró el control de la tensión arterial y tras suspender el minoxidil, la hipertricosis desaparece. (Acta Med Colomb 2014; 39: 191-195). Secondary Hypertension is more common in individuals under 30; most have renovascular etiology; endocrine etiology is exceptional; primary hyperaldosteronism is only responsible for 5-15%, Conn syndrome corresponds to 0.05-2.2 % of the hypertensive population and is one of the few potentially curable causes of hypertension, so we consider this case worthy to be revised. A 63 year old man diagnosed with hypertension 25 years ago and treated with multiple antihypertensives including minoxidil, with uncontrolled blood pressure readings, which consults to endocrinology for appearance of facial hair, is presented. Secondary hypertension was considered, and hypokalemia was found. The ratio of aldosterone and high renin, suggested the presence of hyperaldosteronism which was localized by adrenal venography. Surgical removal of the lesion confirmed the diagnosis of adrenocortical adenoma. After surgery, control of blood pressure improved and after discontinuation of minoxidil, hypertrichosis disappears. (Acta Med Colomb 2014; 39: 191-195).

In recent years, much attention has focused on the role of aldosterone and mineralocorticoid receptors (MRs) in the pathophysiology of hypertension and cardiovascular disease. Patients with primary aldosteronism, in whom angiotensin II levels are low, have a higher incidence of cardiovascular complications than patients with essential hypertension. The Randomized Aldactone Evaluation Study (RALES) demonstrated that adding a non-specific MR antagonist, spironolactone, to a standard therapy that included angiotensin-converting enzyme (ACE) inhibitors, loop diuretics, and digoxin, significantly reduced morbidity and mortality in patients with moderate to severe heart failure. Similarly, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) showed that the addition of a selective MR antagonist (ARM), eplerenone, to an optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. These data suggest that aldosterone induces cardiac injury through activation of MRs and support the notion that MR blockade has beneficial effects on aldosterone-dependent cardiac injury, through mechanisms that cannot be simply explained by hemodynamic changes. Although, MRA are highly effective in patients with heart failure, the risk of hyperkalemia should not be overlooked. Serious hyperkalemia events were reported in some MRA clinical trials; however these risks can be mitigated through appropriate patient selection, dose selection, patient education, monitoring, and follow-up.

In recent years, much attention has focused on the role of aldosterone and mineralocorticoid receptors (MRs) in the pathophysiology of hypertension and cardiovascular disease. Patients with primary aldosteronism, in whom angiotensin II levels are low, have a higher incidence of cardiovascular complications than patients with essential hypertension. The Randomized Aldactone Evaluation Study (RALES) demonstrated that adding a non-specific MR antagonist, spironolactone, to a standard therapy that included angiotensin-converting enzyme (ACE) inhibitors, loop diuretics, and digoxin, significantly reduced morbidity and mortality in patients with moderate to severe heart failure. Similarly, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) showed that the addition of a selective MR antagonist (ARM), eplerenone, to an optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. These data suggest that aldosterone induces cardiac injury through activation of MRs and support the notion that MR blockade has beneficial effects on aldosterone-dependent cardiac injury, through mechanisms that cannot be simply explained by hemodynamic changes. Although, MRA are highly effective in patients with heart failure, the risk of hyperkalemia should not be overlooked. Serious hyperkalemia events were reported in some MRA clinical trials; however these risks can be mitigated through appropriate patient selection, dose selection, patient education, monitoring, and follow-up.

El seudohipoaldosteronismo (PHA) tipo I múltiple es un síndrome de resistencia mineralocorticoide, de herencia autosómica recesiva, que afecta a túbulo renal, glándulas salivales y sudoríparas y mucosa del colon. Caso 1: Recién nacida con hermana que falleció a los 10 días de vida con hiperpotasemia. A los 7 días de vida presenta deshidratación, hiponatremia, hiperpotasemia, acidosis metabólica e hipernatriuria. El diagnóstico se basó en la presencia de aldosterona en plasma, actividad de renina plasmática (ARP) y eliminación de sal en sudor muy elevadas. Precisó rehidratación y tratamiento con sal, bicarbonato, resinas de intercambio iónico y dieta pobre en potasio. Durante el primer año de vida requirió hospitalización por descompensaciones repetidas. Tras 7 años de evolución, aún precisa suplementos de sal y bicarbonate y resinas de intercambio iónico. El desarrollo psicomotor y el crecimiento son adecuados. Caso 2: Recién nacida de 8 días con antecedente de consanguinidad en la familia materna. Al ingreso presenta deshidratación severa con hiponatremia, hiperpotasemia, acidosis metabólica e hipernatriuria, con aldosterona, ARP y sal en sudor muy elevados. Precisa rehidratación, suplementos de sal y bicarbonato y resinas de intercambio iónico. Permanece ingresada durante 6 meses por descompensaciones múltiples, siendo posible posteriormente control ambulatorio. Al año de edad, la curva de peso y el desarrollo psicomotor son adecuados. Conclusiones: Se debe sospechar PHA I múltiple en recién nacidos con síndrome pierdesal e hiperpotasemia, sin virilización, hiperpigmentación ni déficit glucocorticoide, que no responde al tratamiento con mineralocorticoides. La labilidad en el primer año de vida obliga al ingreso hospitalario prolongado. A edades posteriores es susceptible de control ambulatorio. : Multiple type I pseudohypoaldosteronism (PHA-I) is an autosomal recessive condition with multiple target-organ unresponsiveness to aldosterone, manifested early after birth with severe salt-wasting and hyperkalemia. Case 1: Female infant born at term after an uneventful pregnancy. One female sibling died in the first week of life with hyperkalemia. The diagnosis of multiple PHA-I resulted from a picture of dehydratation, hyperkalemia and hyponatremia with increased plasma renin activity (PRA), plasma aldosterone and sweat electrolytes. The treatment consisted of salt and sodium bicarbonate supplements, restricted potassium intake, cation exchange resins and high fluir intale. During first year she was hospitalized for severe salt-losing crises. At 7 years of age, she needs salt and sodium bicarbonate supplements and cation exchange resins. She has a normal growth andneurodevelopment. Case 2: Seven-day female newborn with consanguinity in maternal family. Pregnancy and delivery were uncomplicated. On admission she was severely dehydrated with hyponatremia, hyperkalemia, metabolic acidosis and elevated PRA, plasma aldosterone and sweat electrolytes.She remained hospitalized for six months and she was dependent on high amounts of salt and sodium bicarbonate supplements, fluir intake and cation exchange resins. Growth and neurodevelopment are normal. Conclusions: Multiple PHA-I may be suspected in a newborn with salt-loss and hyperkalemia without glucocorticoid defect. The frequent episodes of dehydratation during the first year of life require long hospitalization. The improvement with age make posible an ambulatory control after the first year of life.

Primary aldosteronism (PA) is a known cause of hypertension. In the kidney, aldosterone promotes sodium and water reabsorption, increasing the intravascular volume and blood pressure (BP). In the cardiovascular system, aldosterone modifies endothelial and smooth muscle cell response, increasing cardiovascular risk in a blood pressure-independent way. Recently a high prevalence of PA (near to 10%) in hypertensive population, has been detected measuring plasma aldosterone/renin activity ratio (ARR) as screening test. This ratio increases along with the severity ofthe hypertensive disease. The diagnostic work up of PA should confirm the autonomy of aldosterone secretion from the renin-angiotensin system and should differentiate the clinical subtypes of the disease. These are idiopathic aldosteronism (IA) and aldosterone-producing adenoma (APA). Other causes are familial hyperaldosteronism (FH) type I (glucocorticoid-remediable aldosteronism), FH-II (non glucocorticoid-remediable aldosteronism), primary adrenal hyperplasia and adrenal carcinoma. This article reviews the prevalence, diagnosis and treatment of PA and also the clinical, biochemical and genetic characteristics ofits different subtypes

Primary aldosteronism (PA) is a known cause of hypertension. In the kidney, aldosterone promotes sodium and water reabsorption, increasing the intravascular volume and blood pressure (BP). In the cardiovascular system, aldosterone modifies endothelial and smooth muscle cell response, increasing cardiovascular risk in a blood pressure-independent way. Recently a high prevalence of PA (near to 10%) in hypertensive population, has been detected measuring plasma aldosterone/renin activity ratio (ARR) as screening test. This ratio increases along with the severity ofthe hypertensive disease. The diagnostic work up of PA should confirm the autonomy of aldosterone secretion from the renin-angiotensin system and should differentiate the clinical subtypes of the disease. These are idiopathic aldosteronism (IA) and aldosterone-producing adenoma (APA). Other causes are familial hyperaldosteronism (FH) type I (glucocorticoid-remediable aldosteronism), FH-II (non glucocorticoid-remediable aldosteronism), primary adrenal hyperplasia and adrenal carcinoma. This article reviews the prevalence, diagnosis and treatment of PA and also the clinical, biochemical and genetic characteristics ofits different subtypes

Background: Adrenal tumor (AT) malignancy has been related to tumor size. Since laparoscopic surgery is being used, smaller adrenal tumors are being excised. Aim: To evaluate eventual clinical and histológica! differences between adrenal tumors smaller than 4 cm. and those larger than 6 cm. Patients and Methods: Retrospective review of pathological reports and clinical records of patients operated for adrenal tumors, dividing them in two groups. Group 1 had 29patients aged 52 ± 13 years with AT < 4 cm operated during the period 2000-2005, and Group 2 was formed by 52 patients aged 46 ±18 years with AT >6 cm operated between 1984-2005- Tumors between 4 and 6 cm were not included in the study to establish clear cut differences between groups. Results: Tumors were functional in 40 and 41% of cases in groups 1 and 2 respectively. Fifty percent of functional tumors of group 1 were pheochromocytomas and the rest secreted aldosterone. In group 2, 66% of tumors were phechromocytomas and no aldosterone secreting tumors were found. Fifty two and eight percent of tumors in Groups 1 and 2 were adenomas, respectively (p

The behavior of 45 canine patients with degeneration to valvular mixomatosa mitral, handled with a combination enalapril- espironolactona (20) or enalapril (25) were evaluated in three occasions during 12 months, making a pursuit of survival, serum levels of aldosterone (marking), creatinine, ureico nitrogen in blood, sodium and potassium.It was observed that aldosterone has a reduction in the serum levels subsequent to the treatment with enalapril and espironolactona far beyond the treated solely with enalapril, but in the last evaluation, they increase the levels over the initial values, which suggests they already have activated other routes for the synthesis from the aldosterone, which are not mediated by angiotensin II and therefore they do not respond suitably to converter enzymes of angiotensin. The benefit of the combination with espironolactone is based on its selective blocking a selective of the aldosterone receivers, which would diminish its lethal action on the myocardium and the blood vessels. El comportamiento de 45 pacientes caninos con degeneración valvular mixomatosa mitral, manejados con una combinación enalapril- espironolactona (20) o enalapril (25) fueron evaluados en tres ocasiones durante 12 meses, realizando un seguimiento de sobrevivencia, niveles séricos de aldosterona (marcador), creatinina, nitrógeno ureico en sangre, sodio y potasio.Se observó que la aldosterona tiene una reducción en los niveles séricos posterior al tratamiento con enalapril y espironolactona muy superior a los tratados únicamente con enalapril, pero en la última evaluación, aumentan los niveles por encima de los valores iniciales, lo que sugiere que ya se han activado otras vías diferentes para la síntesis de la aldosterona, que no están mediados por la angiotensina II y que por tal motivo no responden adecuadamente a las enzimas convertidoras de angiotensina. El beneficio de la combinación con espironolactona se basa en que ésta, es un bloqueador selectivo de los receptores para aldosterona, lo que disminuiría su acción letal sobre el miocardio y los vasos sanguíneos.

Background: Hypertensive states could result from constitutive activation of mineralorticoid receptor (MR) that generates salt retention and blood pressure elevation. Moreover, microsatellite regions can be associated to the regulation of the gene expression, producing subtle pathologies. Aim: To determine the influence of microsatellite marker AGAT of the mineralocorticoid receptor gene in the plasma renin activity (PRA) and serum aldosterone (SA) levels of essential hypertensives (HT). Patients and Methods: We studied 292 HT patients and 57 normotensive (NT) controls. Blood samples were collected for PRA, SA and DNA isolation. Subjects were genotyped according to the length of the tetranucleotide AGAT repeat using polymerase chain reaction and polyacrylamide gel electrophoresis. Based on the normal distribution, we considered 13 to 15 repeats as a habitual (H) length and less than 13 or more than 15 repeats, as non-habitual (non-H). Results: We detected 8 different lengths in the AGAT repeat (allele) in both groups, ranging from 9-17 repeats, where the allele 11 was not detected in either hypertensive or normotensive groups. The allelic distribution was different in both groups (c²=37.57, 4GL, p

Fil: Coppo, José Antonio. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias; Argentina. Se ha propuesto que el retraso del desarrollo del ternero precozmente destetado se debería al estrés producido por dicha maniobra. En tal caso, deberían evidenciarse incrementos plasmáticos de la concentración de aldosterona. Para probar tal hipótesis, se determinaron los valores de dicha hormona en 120 terneros cruza cebú de 2 meses de edad, 50% de cada sexo. Sesenta fueron destetados a los 60–70 días de vida (lote W) y los restantes permanecieron en amamantamiento al pie de madre (lote U). Bajo un diseño de medidas repetidas, aldosterona fue evaluada por radioinmunoanálisis a los días 0 (destete precoz), 7, 14, 21, 28, 60, 90 y 120 (destete convencional). En el día 0 las concentraciones fueron de 348±12 y 351±13 pg/ml, en tanto que en el día 120 fueron de 288±11 y 291±14 pg/ml en U y W respectivamente. Esta tendencia decreciente fue estadísticamente significativa (p < 0,05) y se atribuye a la ontogenia. Sin embargo, en cada fecha de muestreo, no se registraron diferencias significativas entre lotes, alejando la posibilidad de existencia de estrés. It was suggested that the growth delay of early–weaned calf wouldbe attributed to stress. In this case, plasmatic increases of aldosterone concentration shouldhave occurred. To prove this hypothesis, values of this hormone were determined in 120 half–bred zebu calves (2 months old, 50% each sex). Sixty of them were weaned at 60–70 dayspost–partum (lot W), while the rest continued nursing (lot U). Using a repeated measuresdesign, aldosterone was evaluated by radioimmunoassay on days 0 (early weaning), 7, 14, 21,28, 60, 90 and 120 (traditional weaning). Concentrations were 348±12 and 351±13 pg/ml onday 0, as well as 288±11 and 291±14 pg/ml on day 120, in U and W, respectively. This fallingtendency was statistically significant (p < 0.05) and it is attributed to the ontogeny. However,in each sampling date, significant differences between lots were not registered, moving awaythe possibility of stress.

Background: Glucocorticoids play a key role in blood pressure (BP) control and are associated with hypertension in patients with Cushing's syndrome. A number of reports indicate that cortisol (F) may be involved in etiology of essential hypertension (EH). F can bind to the mineralocorticoid receptor, triggering both sodium and water reabsorption in kidney, increase BP and cause renin suppression. Aim: To evaluate urinary free cortisol (UFF) excretion as a potential intermediate phenotype of essential hypertension and correlate F level with plasma renin activity (PRA) and serum aldosterone (SA). Patients and Methods: We recruited 132 EH patients and 16 normotensive healthy controls. Blood samples and 24 hours urine were collected for PRA, SA and UFF analysis. Differences in UFF excretion between sexes were normalized by urinary creatinine (Creat) excretion. The upper limit of UFF/Creat was determined in normotensives considering the mean value plus 2 standard deviations. According to this value, subjects were classified as having high or normal UFF. Results: In EH patients and in normotensives, the UFF/Creat was 36.9±17.0 µg/gr and 30.9±8.8 µg/gr, respectively. The upper limit was set at 48.5 µg/gr. A high UFF/Creat was found in 20/132 EH (15%) patients and 0/16 normotensive subjects. EH patients with high UFF showed lower PRA levels than patients with normal cortisol levels (0.78±0.47 vs. 1.13±0.66 ng/ml*h, respectively, p=0.027) and lower SA values (4.52±1.65 vs 6.34±3.37 ng/dl, respectively, p=0.018). There was a negative correlation between UFF and PRA (r=-0.176, p=0.044) and between UFF and SA (r=-0.183, p=0.036). Conclusions: We have identified a subgroup of EH patients with increased UFF excretion. Patients with the highest UFF showed lower renin and aldosterone levels. These data suggest a potential influence of cortisol in the genesis of hypertension (Rev Méd Chile 2004; 132: 1053-9)

Background: Glucocorticoids play a key role in blood pressure (BP) control and are associated with hypertension in patients with Cushing's syndrome. A number of reports indicate that cortisol (F) may be involved in etiology of essential hypertension (EH). F can bind to the mineralocorticoid receptor, triggering both sodium and water reabsorption in kidney, increase BP and cause renin suppression. Aim: To evaluate urinary free cortisol (UFF) excretion as a potential intermediate phenotype of essential hypertension and correlate F level with plasma renin activity (PRA) and serum aldosterone (SA). Patients and Methods: We recruited 132 EH patients and 16 normotensive healthy controls. Blood samples and 24 hours urine were collected for PRA, SA and UFF analysis. Differences in UFF excretion between sexes were normalized by urinary creatinine (Creat) excretion. The upper limit of UFF/Creat was determined in normotensives considering the mean value plus 2 standard deviations. According to this value, subjects were classified as having high or normal UFF. Results: In EH patients and in normotensives, the UFF/Creat was 36.9±17.0 µg/gr and 30.9±8.8 µg/gr, respectively. The upper limit was set at 48.5 µg/gr. A high UFF/Creat was found in 20/132 EH (15%) patients and 0/16 normotensive subjects. EH patients with high UFF showed lower PRA levels than patients with normal cortisol levels (0.78±0.47 vs. 1.13±0.66 ng/ml*h, respectively, p=0.027) and lower SA values (4.52±1.65 vs 6.34±3.37 ng/dl, respectively, p=0.018). There was a negative correlation between UFF and PRA (r=-0.176, p=0.044) and between UFF and SA (r=-0.183, p=0.036). Conclusions: We have identified a subgroup of EH patients with increased UFF excretion. Patients with the highest UFF showed lower renin and aldosterone levels. These data suggest a potential influence of cortisol in the genesis of hypertension (Rev Méd Chile 2004; 132: 1053-9)

La adrenomedulina (AM) es un péptido hipotensor altamente expresado en el sistema nervioso central. La administración central de AM produce: inhibición de la ingesta de sal, agua y de la secreción de arginina-vasopresina, incremento de los niveles plasmáticos de oxitocina, diuresis y natriuresis En las glándulas suprarrenales la AM inhibe la secreción de aldosterona (ALD) inducida por la angiotensina II, KCL o ACTH. Nosotros evaluamos la hipótesis de la disminución de la actividad mineralocorticoide sobre el riñón como el posible mecanismo responsable del fenómeno natriurético. La AM-IVT incrementó el volumen urinario y la excreción de sodio durante las 6 horas del período de recolección de la orina. En las ratas controles y las depletadas de sodio, los niveles de ALD plasmática permanecieron sin cambios hasta 15 minutos después de la AM-IVT. La natriuresis inducida por la AM-IVT no fue afectada significativamente en la ausencia (ratas ADX) o el exceso de ALD plasmática (SHAM+ALD), o en ratas ADX, con o sin reemplazo hormonal. Nuestros resultados sugieren que la AM juega un papel en la regulación central del balance de fluidos y electrolitos, y que el efecto natriurético de la AM cerebral no está relacionado con los niveles plasmáticos de mineralocorticoides, ni con la presencia de las glándulas suprarrenales. Adrenomedullin (AM) is a hypotensive peptide that is highly expressed in the central nervous system. Central AM increases water and salt intake, arginine-vasopressin secretion and produces diuresis and natriuresis. In adrenal glands AM inhibits aldosterone (ALD) secretion induced by angiotensin II, KCL or ACTH. We assessed the hypothesis that a diminished mineralocorticoid effect on the kidney may explain the natriuretic phenomenon. In control or sodium depleted rats, plasma ALD remained unchanged for up to 15 minutes after AM-IVT. Natriuresis induced by AM-IVT was not significantly affected in the absence (ADX rats) or excess of plasma ALD (SHAM+ALD), or in ADX rats, with or without hormonal treatment. Our results suggest that AM plays a role in the central regulation of water and electrolyte balance, and that AM natriuretic effect is unrelated to mineralocorticoids plasma levels or to the adrenal glands.

Dado que en la síntesis de hormonas esteroides a partir de colesterol participan distintos citocromos P450, que son hemoproteínas, es posible que exista una relación entre la síntesis de esteroides y la de hemo. Con el fin de analizar esta posibilidad, en el presente trabajo se estudió el efecto del agregado de hemina sobre la síntesis de esteroides en adrenales de rata. Se encontró que la adición de hemina in vitro a homogenatos de adrenal o la administración de hemina a ratas in vivo, estimulan la síntesis de esteroides. Por otro lado, 3,5-dietoxicarbonil-1,4-dihidrocolidina, fue capaz de inhibir la síntesis de hemo en adrenal similarmente a lo que ha sido descripto en hígado, por inhibición de la última enzima de esta biosíntesis, la ferroquelatasa. El bloqueo de la síntesis de hemo en adrenal con DDC produjo una disminución de la acumulación de aldosterona y corticosterona producida por ACTH. Este efecto del DDC fue parcialmente revertido por tratamiento de las ratas con hemina. Es decir que el contenido de hemo es un factor limitante de la respuesta de un estimulador de la síntesis de esteroides como ACTH. El fenobarbital, un conocido inductor de la síntesis de hemo, que estimula la transcripción de la enzima regulatoria de esta biosíntesis, el ALA-sintasa, actuando sobre el promotor de este gen que es el mismo que se expresa en adrenal, fue capaz de estimular la síntesis de aldosterona y corticosterona en adrenales de rata. Además, se encontró que estimuladores de la síntesis de esteroides en adrenal, como ACTH y endotelina, son capaces de aumentar el mRNA de ALA-sintasa de modo de asegurar una suficiente provisión de hemo para transformar los apociticromos libres, involucrados en síntesis de esteroides, en holocitocromos activos. Es decir que la disponibilidad de hemo afecta la síntesis de esteroides y los estimuladores de la síntesis de esteroides aumentan el mRNA de ALA-s para asegurar esta disponibilidad. También en este trabajo se investigó la participación de glicosilfosfatidilinositol (GPI) en la respuesta de ACTH. Teniendo en cuenta que se había informado que ACTH estimula una fosfolipasa C que hidroliza GPI, lo que libera inositolfosfoglicano (IGP), que es capaz de inhibir la acumulación de esteroides mediada por ACTH y que ACTH estimula la liberación al medio extracelular de fosfatasa alcalina, una enzima anclada a la superficie celular por GPI; se quiso investigar si la liberación de fosfatasa alcalina por ACTH está mediada por una fosfolipasa C que hidroliza GPI y el mecanismo involucrado en la activación de esta fosfolipasa. Se encontró que ACTH a través de AMPc activa una Gi que es necesaria para la activación de una fosfolipasa C de GPI involucrada en la liberación de fosfatasa alcalina por la hormona. Es decir que el receptor de ACTH, como ha sido descripto con otros receptores acoplados a Gs que estimulan la producción de AMPc, es capaz de producir un posterior acoplamiento a Gi mediado por AMPc. Este acoplamiento a Gi media la activación de una fosfolipasa C de GPI lo que produce IPG que, como se había visto, es capaz de inhibir la respuesta de la hormona. Por lo tanto, la respuesta de ACTH se inicia con un acoplamiento a Gs y posteriormente un acoplamiento a Gi que mediaría una señal de apagado de la respuesta. Since different cytochromes P450, which are hemeproteins, are involved in steroid biosynthesis; an interdependence between heme and steroid biosynthesis might occur. In order to evaluate this possibility, the effect of the addition of hemin on steroid biosynthesis in rat adrenals was investigated. It was found that in vitro addition of hemin to adrenal homogenates as well as hemin administration to rats in vivo increase steroid production. On the other hand, DDC, 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine, was able to inhibit heme biosynthesis in adrenal in a way similar to that reported for liver, by inhibiting the last step in heme biosynthesis, ferrochelatase activity. The blockage of heme biosynthesis in adrenal with DDC provoked a decrease in ACTH-mediated aldosterone and corticosterone accumulation. The effect of DDC was partially reversed by ACTH treatment. Thus adrenal heme content is limiting the response of an stimulator of steroid synthesis such as ACTH. Phenobarbital, a known activator of heme synthesis, which stimulates the transcription of the regulatory enzyme of this pathway, ALA-synthase, upon activation of the promotor of this gene that is also expressed in adrenal, was able to increase aldosterone and corticosterone synthesis in rat adrenal. In addition, it was found that simulators of steroid biosynthesis, such as ACTH and endothelin, were able to increase, the mRNA of ALA-synthase, in order to provide enough heme to transform steroidogenic apocytochromes into active holocytochromes. In conclusion, heme availability affects steroid biosynthesis and stimulators of steroid biosynthesis increase ALA-synthase mRNA to ensure this availability. It was also investigated the involvement of glycosylphosphatidylinositol (GPI) in ACTH action. Taking into account that it was reported that ACTH activates a GPI-phospholipase C releasing inositolphosphoglycan (IPG) which inbhibits ACTH-mediated steroid accumulation and that ACTH increases the release to the extracellular medium of a GPI-anchored protein, alkaline phosphatase; the involvement of GPI-phospholipase C on the release of this enzyme by the hormone and its mechanism of activation was evaluated. It was found that ACTH through cAMP activates Gi, which mediates the activation of a GPI-phospholipase C that releases alkaline phosphatase. Thus ACTH receptor, as it was reported for other Gs-coupled receptors which increase cAMP production, is able to couple to Gi and the switch is mediated by cAMP. Once coupled to Gi, ACTH receptor activates a GPI-phospholipase C which in turn produce IPG that is able to inhibit ACTH action. ACTH action is initiated by coupling to Gs, then cAMP-mediated switch to Gi occurs, which signals to turn off the response. Fil: Martini, Claudia Noemí. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.

Based on two patients, we discuss the difficulties in diagnosing and managing primary aldosteronism in pregnancy, which derive from changes of the renin-angiotensin-aldosterone axis, from the uncertainty regarding blood pressure control along gestation and postpartum, and from the contraindication to the use of spironolactone. The first case is a 27 years old woman with a long standing refractory hypertension, a hemorrhagic stroke with left brachial hemiplegia and crural hemiparesia, two miscarriages, one stillbirth and one offspring with intrauterine growth retardation. Due to hypokalemia, a plasma aldosterone/renin activity ratio of 91, and a negative genetic screening for glucocorticoid remediable aldosteronism (GRA), a primary hyperaldosteronism with normal adrenals in CT scan was diagnosed, and good blood pressure control was attained with spironolactone. After two and a half years of normotension, a fifth pregnancy, managed with methyldopa evolved with satisfactory blood pressures, plasma potassium, fetal growth, uterine and umbilical arterial resistance indexes, and maternal endothelial function. At 37 1/2 weeks of pregnancy the patient delivered a healthy newborn weighing 2,960 g. Blood pressure rose during the 48 hours of postpartum in the absence of proteinuria and required iv hydralazine. The second patient is a 37 years old woman, with known refractory hypertension for 7 years, hypokalemia, plasma aldosterone/renin activity ratio greater than 40, normal adrenals in the CAT scan, and a negative genetic screening for GRA. She had normotensive pregnancies 5 and 3 years prior to the detection of hypertension, with hypertensive crisis in both postpartum periods, retrospectively considered as expressions of primary hyperaldosteronism (Rev Méd Chile 2002; 130: 1399-1405)

Based on two patients, we discuss the difficulties in diagnosing and managing primary aldosteronism in pregnancy, which derive from changes of the renin-angiotensin-aldosterone axis, from the uncertainty regarding blood pressure control along gestation and postpartum, and from the contraindication to the use of spironolactone. The first case is a 27 years old woman with a long standing refractory hypertension, a hemorrhagic stroke with left brachial hemiplegia and crural hemiparesia, two miscarriages, one stillbirth and one offspring with intrauterine growth retardation. Due to hypokalemia, a plasma aldosterone/renin activity ratio of 91, and a negative genetic screening for glucocorticoid remediable aldosteronism (GRA), a primary hyperaldosteronism with normal adrenals in CT scan was diagnosed, and good blood pressure control was attained with spironolactone. After two and a half years of normotension, a fifth pregnancy, managed with methyldopa evolved with satisfactory blood pressures, plasma potassium, fetal growth, uterine and umbilical arterial resistance indexes, and maternal endothelial function. At 37 1/2 weeks of pregnancy the patient delivered a healthy newborn weighing 2,960 g. Blood pressure rose during the 48 hours of postpartum in the absence of proteinuria and required iv hydralazine. The second patient is a 37 years old woman, with known refractory hypertension for 7 years, hypokalemia, plasma aldosterone/renin activity ratio greater than 40, normal adrenals in the CAT scan, and a negative genetic screening for GRA. She had normotensive pregnancies 5 and 3 years prior to the detection of hypertension, with hypertensive crisis in both postpartum periods, retrospectively considered as expressions of primary hyperaldosteronism (Rev Med Chile 2002; 130: 1399-1405)

Background: Half of hypertensive patients with low plasma renin activity have a primary hyperaldosteronism. Among the remaining half, 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD2) deficiency plays an important role. This enzyme catalyzes the conversion of cortisol to cortisone, avoiding the interaction of cortisol with the mineralocorticoid receptor. If the enzyme fails, cortisol will stimulate sodium and water reabsorption and increase blood pressure. Aim: To determine biochemical alterations, suggestive of 11ßHSD2 deficiency, in low-renin hypertensive patients. Patients and Methods: Twenty eight hypertensive patients with a plasma renin activity of less than 0.5 ng/ml/h and with a plasma aldosterone of less than 5 ng/dl were studied. Twenty eight normotensive patients were studied as controls. Serum cortisol (RIA), cortisone (ELISA) and the serum cortisol/cortisone ratio were determined in all of them, between 9 and 10 AM. Measurements were confirmed by high pressure liquid chromatography. The serum cortisol/cortisone ratio was considered abnormal when its Ln (cortisol/cortisone) value was over 2 standard deviations of the mean. Results: Serum cortisol was higher in hypertensive subjects than in controls (11.1±3.3 and 9.2±2.8 µg/dl, respectively; p

Background: Primary hyperaldosteronism is more frequent among subjects with essential hypertension than previously thought. The prevalence, according to local and international evidence could fluctuate between 9 and 10%. Aim: To investigate if subjects with essential hypertension have different aldosterone and renin plasma levels than normotensive subjects. Patients and methods: One hundred twenty five subjects with essential hypertension, not receiving medications for at least two weeks prior to the study and 168 age and sex matched normotensive controls were studied. Blood was drawn between 9 and 10 AM during a sodium free diet to determine plasma aldosterone, plasma renin activity and potassium. Results: Plasma aldosterone was higher in hypertensive subjects than controls (11.6 ± 7.6 and 9.9 ± 5.1 ng/dl respectively; p=0.04). Plasma renin activity was lower in hypertensives than controls (1.42 ± 1.28 and 1.88 ± 1.39 ng/ml/h respectively; p