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Alteraciones vasculares en la insuficiencia renal crónica. Papel del endotelio.

Source: OAI

ABSTRACT RESUMEN El síndrome urémico resulta de la disminución marcada de la función renal. Este estado mantenido conduce a la insuficiencia renal crónica, que se define como la destrucción progresiva e irreversible de las nefronas. En la insuficiencia renal crónica se dan cita diferentes factores de riesgo cardiovascular, la propia uremia supone un factor de riesgo. La causa principal de morbi-mortalidad en estos pacientes deriva de alteraciones en el sistema cardiovascular. El tratamiento mediante hemodiálisis ha supuesto la prolongación de la vida para estos enfermos, pero a la vez, ha acarreado problemas relacionados con alteraciones cardiovasculares. En la presente tesis se estudian las vías de síntesis de factores endoteliales que pueden estar alteradas por la enfermedad y que pueden ser las responsables, al menos en parte, de las alteraciones vasculares que padecen estos enfermos. Nos centramos en la participación de los factores endoteliales relajantes: prostaciclina, NO y EDHF, observando que la uremia produce una disminución de su síntesis o liberación en respuesta a estímulos vasodilatadores y vasoconstrictores. Las alteraciones vasculares que puede ocasionar el tratamiento con hemodiálisis, ha puesto de manifiesto que aunque disminuye la participación de NO en la respuesta vascular, aumenta la de EDHF. Estos resultados son importantes, pues suponen la aparición de un mecanismo compensatorio, capaz de mejorar la función endotelial. El estudio de la expresión de genes implicados de manera directa o indirecta en la reactividad vascular sugiere que la enfermedad podría tener su origen en un fallo metabólico, puesto que nuestros resultados muestran una menor expresión génica de DDAH-1. Esta enzima es la encargada de metabolizar las toxinas que se acumulan en la uremia y que son inhibidores enzimáticos, causando gran parte de la disfunción vascular y alteraciones neurológicas que aparecen en esta enfermedad. Las modificaciones enzimáticas que hemos observado en la insuficiencia renal crónica podrían ser dianas terapéuticas para mejorar la calidad de vida en estos enfermos. __________________________________________________________________________________________________ Uremia is an established risk factor for cardiovascular and cerebrovascular accidents. Hemodialysis improves the lifes quality of these patients, but this treatment also produces vascular alterations. We examined the relaxant and contractile response in forearm veins from patients with chronic renal failure before hemodialysis, on chronic hemodialysis and in veins obtained from donors (controls). We study the role of vasodilator prostaglandins (PGI2), nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF). The contribution of these factores is diminished in chronic renal failure. This effect might contribute to, or even cause, some of the vascular features of this condition. Hemodialysis improves the endothelial function because of an augmented participation of EDHF. The study of gene expression showed a metabolic failure in the enzyme that degrades the uremic toxins. The low expression of this enzyme, dimethylarginine dimethylamino hydrolase (DDAH), could explain some vascular features and could be a therapeuthic strategy for improving lifes quality of these patients.

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