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La hipercontracción inducida por la serotonina a través de los receptores de 5-hidroxitriptamina 1B en las arterias

T Ishida¹, S Kawashima, Hirata Ki

¹First Department of Internal Medicine and Institute for Experimental Animals, Kobe (Japan) University School of Medicine.

|March 10, 2001

Resumen

La aterosclerosis aumenta las contracciones inducidas por la serotonina en las arterias coronarias del conejo, principalmente a través de los receptores 5-HT1B regulados hacia arriba. Este mecanismo implica una mayor movilización de calcio y contribuye a la isquemia miocárdica.

Área de la Ciencia:

Biología Cardiovascular Biología Cardiovascular
Farmacología Farmacología.
Investigación de la aterosclerosis Investigación de la aterosclerosis.

Sus antecedentes:

El aumento de la vasoconstricción a la serotonina (5-hidroxitriptamina [5-HT]) en los vasos ateroscleróticos contribuye a la isquemia miocárdica.
Se investigaron los mecanismos subyacentes a la hipercontracción evocada por la serotonina en las arterias coronarias de conejos ateroscleróticos.

Objetivo del estudio:

Para dilucidar los mecanismos responsables del aumento de la vasoconstricción inducida por la serotonina en las arterias coronarias ateroscleróticas.
Identificar los subtipos específicos de los receptores de serotonina y las vías de señalización involucradas en esta hipercontracción.

Principales métodos:

Examinó las respuestas contráctiles a los agentes serotoninérgicos en las arterias coronarias endotelialmente denudadas de conejos con hiperlipidemia hereditaria (WHHL) de control y Watanabe.
Se utilizaron antagonistas de los receptores 5-HT ((1B/1D) y 5-HT ((2), toxina de la tos ferina y se midieron los niveles de calcio intracelular ([Ca ((2+) ]) y de ARNm.

Principales resultados:

Las arterias coronarias WHHL mostraron hipercontracción a los agonistas del receptor 5-HT1 con concentraciones de umbral más bajas y mayores respuestas máximas.
Las contracciones evocadas por la serotonina fueron inhibidas por un antagonista de 5-HT ((1B / 1D) y la toxina de la tos ferina, pero no por un antagonista de 5-HT ((2).
La hipercontracción correlacionada con el aumento de la elevación [Ca2+] y los niveles de ARNm 5-HT1B fueron significativamente regulados hacia arriba en las arterias WHHL.

Conclusiones:

Las arterias coronarias de conejos ateroscleróticos exhiben una mayor contracción y movilización de calcio en respuesta a la serotonina.
El receptor 5-HT1B, regulado al alza en la aterosclerosis, es el probable mediador de los efectos de aumento de la serotonina.
Estos hallazgos ponen de relieve el papel de la regulación del receptor 5-HT ((1B) en la vasoconstricción mediada por la serotonina durante la aterosclerosis.

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