Verónica De Luca Sarobe

Efecto del alendronato sobre el perfil de citoquinas y metaloproteinasas 2 y 9 en un modelo múrido de artritis experimental

Resumen Introduccion La artritis es una de las artropatias mas frecuentes, se caracteriza por el dano que produce en el cartilago articular y la resorcion osea subcondral. El diagnostico temprano es de crucial importancia para instaurar una terapia preventiva, ya que, en ocasiones, la enfermedad es diagnosticada al presentarse lesiones oseas de dificil resolucion. Objetivos Caracterizar, en un modelo murido de artritis experimental producida por adyuvante, el perfil de distintos biomarcadores articulares, interleuquinas (IL-4, IL-6 y TNF-α) y metaloproteasas (MMP-2 y MMP-9), que permitan seguir la evolucion de la enfermedad y analizar sus diferencias, al aplicar el tratamiento con alendronato en forma preventiva o curativa. Materiales y metodos El alendronato, en forma preventiva, se aplico el dia 0 y de manera curativa a los dos meses posadyuvante. Se realizo un puntaje de los sintomas clinicos; al sacrificio, se determinaron los marcadores articulares y se realizaron los estudios histopatologicos y radiograficos. Resultados Lo mas destacable fue que el grupo que recibio el alendronato, de manera preventiva, alcanzo un puntaje clinico normal de manera mas temprana que el grupo control con adyuvante. Asimismo, los animales tratados con alendronato presentaron valores significativamente mas bajos de metaloproteasas. Conclusiones Nuestros resultados sugieren que, aparentemente, el alendronato disminuye la actividad de proteasas vinculadas a la fisiopatologia de la enfermedad articular, lo cual podria resultar sumamente beneficioso para la terapeutica a instaurar.

Urinary Kallikrein and Blood Pressure – Gender-Different Response to Potassium Supplementation in SHR

Aims: To test whether blood pressure is affected by potassium supplementation which modifies urinary kallikrein (UK) in SHR of either sex, and to elucidate the mechanisms involved. Design: In SHR and WKY blood pressure, renal function and hormonal profile were studied after 1% oral potassium supplementation starting at 4 weeks of age and throughout until 12 weeks of age. Results were compared with those of untreated SHR and WKY of either sex. Results: Systolic blood pressure (mm Hg) started to rise in SHR and was significantly different at 6–8 weeks of age: 153.5 ± 7.9 versus 100 ± 5.6 in female and 157 ± 7.7 versus 98.4 ± 6.8 in male rats (p < 0.01). Systolic blood pressure increased progressively in female and male rats reaching 164.5 ± 4.8 and 204.5 ± 7.6, respectively, at 12 weeks of age. At this time systolic blood pressure was higher in male than in female SHR (p < 0.01) and UK activity (UKa; nkat/day/100 g body weight) was slightly lower in male SHR. After 1% oral potassium supplementation administered from 4 to 12 weeks of age, a decrease in systolic blood pressure was seen in male SHR: 204.5 ± 7.6 versus 173.5 ± 7.9 (p < 0.05); and 164.5 ± 4.8 versus 156.8 ± 5.5 in female rats (NS) at 12 weeks of age, concomitant with an increase in UKa, particularly in male rats (29.35 ± 1.92 versus 36.54 ± 2.61, p < 0.05). As expected, plasma aldosterone (pg/ml), increased markedly after potassium treatment from 129 ± 31.4 in untreated female and male SHR and WKY to 528 ± 180.7 in SHR and 473 ± 88.4 in WKY (p < 0.05 in both cases). After potassium supplementation, potassium excretion was significantly correlated with both aldosterone levels and UKa (p < 0.001 in both cases). No significantly concurrent changes in plasma renin activity were observed, but instead a significant decrease was seen in SHR (p < 0.01). The potassium blood pressure-lowering effect was blunted by aldosterone receptor antagonist treatment that also decreased UKa from 36.5 ± 2.61 to 19.5 ± 1.9, particularly in male SHR. No attempt was made in this experimental setting to block kallikrein or kinin receptors. Conclusions: UKa increases as a consequence of aldosterone stimulation by potassium load since an aldosterone receptor blockade abolishes UKa increment and blood pressure fall. These results further support the hypothesis that the kallikrein kinin system plays a role in blood pressure regulation and they also show a gender different response to potassium load in relation to UKa and blood pressure.

Effect of prepuberal gonadectomy upon aldosterone levels in female and male SHR: interaction between blood pressure and kallikrein kinin system.

It has been suggested that an abnormal activity of the hypothalamic-pituitary-adrenal-gonadal axis may be implicated in the pathogenesis of spontaneously hypertensive rats (SHR) blood pressure hypertension. However, it is widely known that the kallikrein-kinin system plays a role in blood pressure regulation in this strain, because an inverse relation between blood pressure and urinary kallikrein excretion has been reported. It was of our interest to study how early suppression of sexual hormones affected blood pressure regulation in SHR and urinary kallikrein excretion and to elucidate the involved mechanisms. For these purpose, SH and Wistar-Kyoto (WKY) rats blood pressure, renal function, and hormonal profile were studied after prepuberal gonadectomy starting at 4 weeks of age throughout until the 12th week of age. Results were compared with those of untreated SH and WKY rats of either sex. The response to blocking agents against aldosterone and kallikrein-kinin system also were evaluated. Systolic blood pressure increased progressively in male and female SHR 12 weeks of age. Systolic blood pressure was higher in male than in female SHR, but urinary kallikrein was lower in male SHR. Prepuberal gonadectomy induced a significant decrease in systolic blood pressure in male and in female SHR at 12 weeks of age, accompanied by an increase in urinary kallikrein in male and in female SHR. Plasma aldosterone increased markedly in female and male SHR after gonadectomy. No concurrent changes in plasma renin activity or corticosterone levels were observed. The aldosterone receptor antagonist and the kallikrein inhibitor treatment blunted the blood pressure lowering effect of gonadectomy and diminished urinary kallikrein excretion. Results support the existence of a sexual dimorphism related to hypertension and urinary kallikrein and suggest an interaction among the kallikrein-kinin system, sexual hormones, and mineralocorticoids in the neonatal programming of hypertension.