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El ácido fólico previene la disfunción de la sintasa de óxido nítrico inducida por nitroglicerina y la tolerancia a
T Gori1, J M Burstein, S Ahmed
1Division of Cardiology, Department of Medicine, Mount Sinai Hospital, and the University of Toronto, Toronto, Canada.
Circulation
|September 6, 2001
Resumen
La suplementación con ácido fólico evitó la disfunción endotelial inducida por la nitroglicerina y la tolerancia a los nitratos en voluntarios sanos. Esto sugiere que la biodisponibilidad de la tetrahidrobiopterina es clave para la función de la óxido nítrico sintasa y la tolerancia al nitrato.
Área de la Ciencia:
- Farmacología Cardiovascular Farmacología Cardiovascular
- La función endotelial es la función endotelial.
- La señalización del óxido nítrico.
Sus antecedentes:
- El tratamiento continuo con nitroglicerina (GTN) perjudica la función de la óxido nítrico sintasa (NOS), posiblemente debido a la reducción de la biodisponibilidad de la tetrahidrobiopterina (BH4).
- El ácido fólico está implicado en la regeneración de BH4 en varios estados de enfermedad.
- El papel del ácido fólico en la prevención de la disfunción y la tolerancia NOS inducida por GTN requiere investigación.
Objetivo del estudio:
- Para investigar si la administración de ácido fólico previene la disfunción NOS inducida por GTN.
- Para determinar si la suplementación con ácido fólico previene el desarrollo de tolerancia a GTN.
Principales métodos:
- Un estudio doble ciego, controlado con placebo, en el que participaron 18 voluntarios varones sanos.
- Los participantes recibieron ácido fólico oral (10 mg/día) o placebo durante una semana, junto con GTN transdérmico continuo.
- El flujo sanguíneo del antebrazo se midió mediante pletismografía en respuesta a los agentes vasoactivos.
Principales resultados:
- La administración de ácido fólico evitó la disfunción endotelial inducida por GTN, evidenciada por respuestas conservadas a la acetilcolina y la N-monometil-L-arginina.
- Los sujetos que recibieron ácido fólico mostraron respuestas significativamente mayores a la GTN intraarterial en comparación con el grupo placebo.
- La suplementación con ácido fólico mitigó la tolerancia a los nitratos.
Conclusiones:
- El ácido fólico suplementario previene eficazmente tanto la disfunción NOS como la tolerancia a los nitratos inducida por la GTN continua en individuos sanos.
- Se supone que la reducción de la biodisponibilidad de BH4 es un mecanismo central en estos fenómenos.
- Los hallazgos apoyan el papel del estrés oxidativo en la patogénesis de la tolerancia a los nitratos.
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