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La inhibición selectiva de la recaptación de norepinefrina como modelo humano de intolerancia ortostática
Christoph Schroeder1, Jens Tank, Michael Boschmann
1Clinical Research Center, HELIOS Klinkum-Berlin, Germany. jordan@fvk-berlin.de
Circulation
|January 24, 2002
Resumen
El bloqueo de la función del transportador de norepinefrina (NET) con reboxetina imitaba la intolerancia ortostática idiopática en sujetos sanos. Esto sugiere que el deterioro de la absorción de norepinefrina contribuye a las enfermedades cardiovasculares y puede ayudar a prevenir las reacciones vasovágicas.
Área de la Ciencia:
- Fisiología cardiovascular fisiología cardiovascular.
- Neurofarmacología y Neurofarmacología.
Sus antecedentes:
- Las mutaciones funcionales en el gen transportador de norepinefrina (NET) están relacionadas con la intolerancia ortostática idiopática.
- La disminución de la recaptación de norepinefrina es un factor potencial que contribuye a esta condición.
Objetivo del estudio:
- Para investigar los efectos cardiovasculares del bloqueo selectivo del transportador de norepinefrina (NET) en individuos sanos.
- Para determinar si el bloqueo NET replica el fenotipo de la intolerancia ortostática idiopática.
Principales métodos:
- Un estudio aleatorizado, doble ciego y cruzado que involucró a 18 sujetos sanos.
- La administración de un bloqueador de NET selectivo (reboxetina) o un placebo.
- Evaluación de las respuestas cardiovasculares durante las pruebas de presión en frío, las pruebas de agarre y las pruebas de inclinación de cabeza hacia arriba (HUT).
Principales resultados:
- La reboxetina aumentó significativamente la frecuencia cardíaca durante la HUT en comparación con el placebo (P<0.0001).
- La presión arterial media se elevó ligeramente con reboxetina, pero las respuestas de la presión arterial a las pruebas de esfuerzo se atenuaron.
- La reboxetina aumentó la sensibilidad al isoproterenol y la fenilefrina, y redujo las reacciones vasovágicas.
Conclusiones:
- El bloqueo NET selectivo induce un fenotipo cardiovascular similar a la intolerancia ortostática idiopática.
- Esto apoya la hipótesis de que la recaptación desordenada de norepinefrina contribuye a la enfermedad cardiovascular humana.
- La inhibición de NET puede ser una estrategia potencial para prevenir las reacciones vasovágicas.
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