Hypertension in transgenic mice with brain-selective overexpression of the alpha(2B)-adrenoceptor.
Am J Hypertens
; 22(1): 41-5, 2009 Jan.
Article
en En
| MEDLINE
| ID: mdl-18989257
BACKGROUND: Previous studies have shown that the presynaptic alpha(2B)-adrenoceptor subtype in the central nervous system has a sympathoexcitatory function and its activation leads to a hyperadrenergic hypertensive state. The purpose of this project was to develop a novel hyperadrenergic model, a transgenic (TG) mouse model with brain-selective overexpression of the alpha(2B)-adrenergic receptor (alpha(2B)-AR). METHODS: We used Southern blot analysis to confirm transgene, real-time PCR to assess gene expression, western Blot analysis and immunohistology to assess protein expression and localization in brain areas. Indirect blood pressure (BP) and heart rate were recorded. RESULTS: In TG mice there was a 1.8-fold increase in alpha(2B)-AR protein expression compared to wild-type (WT) mice. Immunostaining of brain sections revealed that concentration of alpha(2B)-AR was much more pronounced in TG than in WT mice. Systolic BP at 8 weeks of age was significantly elevated in TG 130 +/- 6 mm Hg, compared with WT control nontransgenic littermates of the same age 107 +/- 7 mm Hg, (P < 0.05), indicating that the TG mice had indeed developed hypertension. CONCLUSIONS: We have therefore documented that overexpression of the alpha(2B)-AR gene leads to increased production of alpha(2B)-AR protein in brain regions known to regulate central sympathetic outflow, thus resulting in sustained BP elevation. This is a unique model of experimental hypertension driven purely by overexpression of the alpha(2B)-AR that would result in an overactive sympathetic system and would be suitable for testing the pharmacologic properties of potential therapeutic agents.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN
/
Expresión Génica
/
Receptores Adrenérgicos alfa 2
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Hipertensión
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Hypertens
Asunto de la revista:
ANGIOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos