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Los ratones con deficiencia del transportador de norepinefrina presentan una taquicardia excesiva y una presión
Nancy R Keller1, André Diedrich, Martin Appalsamy
1Autonomic Dysfunction Center, Department of Medicine, Nashville, TN 37232-2195, USA.
Circulation
|September 1, 2004
Resumen
La deficiencia del transportador de norepinefrina (NET) en ratones conduce a una presión arterial y frecuencia cardíaca elevadas, especialmente durante la actividad. La inhibición simpática central ayuda a mantener los niveles normales de reposo, pero la activación simpática amplifica la señalización periférica.
Área de la Ciencia:
- Fisiología cardiovascular fisiología cardiovascular.
- El transporte de neurotransmisores es el transporte de neurotransmisores.
- Regulación del sistema nervioso autónomo regulación del sistema nervioso autónomo
Sus antecedentes:
- La norepinefrina (NE) es un neurotransmisor clave para la regulación autónoma y la función del nervio simpático.
- El transportador de norepinefrina (NET) regula la señalización NE y es el objetivo de varios medicamentos.
- La disfunción NET está relacionada con problemas cardiovasculares como la intolerancia ortostática.
Objetivo del estudio:
- Para investigar las consecuencias cardiovasculares de la disminución de la recaptación de norepinefrina.
- Para evaluar el papel del transportador de norepinefrina (NET) en el mantenimiento de la homeostasis cardiovascular.
- Examinar el impacto de la deficiencia de NET en la regulación autónoma in vivo.
Principales métodos:
- Monitoreo telemétrico de ratones con deficiencia de NET (NET(-/-)) y de tipo silvestre (NET(+/+).
- Medición de los parámetros cardiovasculares, incluida la presión arterial media y la frecuencia cardíaca.
- Análisis de los niveles plasmáticos de catecolaminas (NE, epinefrina, dopamina) y otros catecolos.
Principales resultados:
- Los ratones NET ((-/-) presentaron una presión arterial media y una frecuencia cardíaca en reposo elevadas en comparación con los controles.
- Los parámetros cardiovasculares aumentaron significativamente en los ratones NET(-/-) durante la actividad.
- Los niveles plasmáticos de NE fueron más altos, mientras que los niveles de dihidroxifenilglicol fueron más bajos en ratones NET, lo que indica una reducción de la recaptación de NE.
Conclusiones:
- La deficiencia de NET da como resultado una función cardiovascular alterada, con presión y frecuencia cardíacas elevadas, particularmente durante la activación simpática.
- La inhibición de la simpatía central puede compensar la deficiencia de NET en reposo, pero esta modulación se supera durante la actividad.
- Los hallazgos destacan el papel crítico de NET en la regulación de la señalización catecolaminergica periférica y la estabilidad cardiovascular.
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