Actividad antioxidante de la adrenomedulina en el vermis cerebeloso de la rata hipertensa: efecto de la amlodipina

Leticia Figueira, Anita Israel

Resumen


La adrenomedulina (AM) es un péptido ubicuo presente en el cerebelo, que participa en la regulación de la presión arterial (PA) y ejerce acciones antioxidantes. El sistema AM-cerebeloso se encuentra alterado durante la hipertensión. Se evaluó el efecto de la reducción de la PA, sobre la acción antioxidante de la AM cerebelosa mediante el uso de amlodipina. Se determinó la producción de sustancias que reaccionan con el ácido tiobarbitúrico (TBARS) y la actividad de las enzimas antioxidantes, superóxido dismutasa (SOD), catalasa (CAT) y glutatión peroxidasa (GPx) durante la hipertensión. Ratas SHR y WKY adultas, recibieron amlodipina (5mg/Kg/día, p.o.) o vehículo, durante once días. Las ratas fueron sacrificadas, se disecó el corazón y el vermis cerebeloso. Se determinó el tamaño del corazón, diámetro de los miocitos y la PA antes y al final del tratamiento. Se estimuló el vermis in vitro con AM. Se homogeneizó, centrifugó el tejido y determinó la concentración de proteínas, la producción de TBARS y la actividad SOD, CAT y GPx. La AM redujo la producción de TBARS y la actividad basal de CAT, GPx y SOD en ratas WKY más no en las SHR. El tratamiento con amlodipina disminuyó el tamaño del corazón, el diámetro de los miocitos, la PA y restituyó la capacidad antioxidante de la AM en ratas SHR. Estos resultados apoyan el papel de la AM cerebelosa como regulador de las enzimas antioxidantes y su alteración en la hipertensión y sugieren un papel de la AM cerebelosa en el control de la PA.


Abstract

Adrenomedullin (AM) is a ubiquitous peptide which is present in the cerebellum. There is evidence that cerebellar AM participates in blood pressure (BP) regulation and exerts antioxidant actions. Cerebellar AM-system is altered during hypertension. Therefore, in this study we assessed the effect of blood pressure reduction with amlodipine on the antioxidant action of cerebellar AM. Thiobarbituric acid reactive substances (TBARS) production and antioxidant enzymes activity, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) was assessed during hypertension. Adult SHR and WKY rats were divided into two groups receiving amlodipine (5 mg/kg/day, p.o.) or vehicle, for eleven days. The rats were sacrificed, the heart and cerebellar vermis were dissected, and heart weight, miocyte diameter and BP was determined before and at the end of treatment.  Cerebellar vermis was stimulated in vitro with AM. Tissue was homogenized and centrifuged and tissue protein concentration, TBARS production and activity of SOD, CAT and GPx determined. Our results demonstrate that AM reduced TBARS production and basal CAT, GPx and SOD activity in WKY rats but not in SHR. Treatment with amlodipine reduced heart weight, myocyte diameter and BP; and reversed the lack of AM antioxidant activity in SHR rats. These results support the role of AM as a regulator of antioxidant enzymes in rat cerebellum and its dysregulation during hypertension, and suggests a role for cerebellar AM in BP control.

Keywords: Adrenomedullin; hypertension; antioxidant enzymes; blood pressure.


Palabras clave


Adrenomedulina; hipertensión; enzimas antioxidantes; presión arterial.

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Referencias


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DOI: https://doi.org/10.25009/eb.v7i14.2579

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