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La disfunción coronaria inducida por aldosterona en ratones transgénicos involucra los canales de potasio activado
Marie-Lory Ambroisine1, Julie Favre, Patricia Oliviero
1Inserm U689 and Paris Diderot University, Paris, France.
Circulation
|November 7, 2007
Resumen
La sobreexpresión de aldosterona en ratones redujo los canales de potasio activado por calcio (BKCa) en los vasos sanguíneos, perjudicando la relajación coronaria. Esto sugiere que los canales BKCa son un objetivo terapéutico potencial para las enfermedades cardiovasculares.
Área de la Ciencia:
- Fisiología cardiovascular fisiología cardiovascular.
- Biología Molecular Biología Molecular
- Farmacología Farmacología.
Sus antecedentes:
- La sobreexpresión de la aldosterona sintasa en los cardiomiocitos causa una disfunción coronaria independiente del óxido nítrico.
- Los canales de potasio activado por calcio (BKCa) son cruciales para la relajación de las células del músculo liso vascular (VSMC).
Objetivo del estudio:
- Investigar si la aldosterona altera la expresión o la función del canal BKCa en los CMVV.
- Determinar el papel de los canales BKCa en la disfunción coronaria inducida por la aldosterona.
Principales métodos:
- Se utilizaron segmentos aislados de la arteria coronaria del ratón en la miografía por alambre.
- Se evaluó la relajación inducida por acetilcolina con y sin varios inhibidores (diclofenaco, caribdotoxina, apamina, iberiotoxina).
- La expresión del canal BKCa se cuantificó en el corazón y las arterias coronarias a través de qPCR y Western blot; los efectos también se estudiaron en VSMCs aórticos de ratas cultivadas.
Principales resultados:
- La relajación coronaria mediada por acetilcolina se redujo significativamente en ratones MAS y fue prevenida por la espironolactona.
- La expresión de las subunidades del canal BKCa (alfa y beta1) se redujo en el corazón y las arterias coronarias de los ratones MAS.
- La aldosterona disminuyó la expresión de BKCa en los VSMC cultivados, un efecto bloqueado por la espironolactona.
Conclusiones:
- La sobreexpresión de aldosterona altera la expresión de BKCa en el VSMC y la relajación coronaria dependiente de BKCa.
- Estas alteraciones pueden contribuir a los efectos perjudiciales de la aldosterona en las enfermedades cardiovasculares.
- Los canales BKCa representan un objetivo terapéutico potencial para las afecciones cardiovasculares.
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