Title

Angiotensin II AT1 receptor blockade selectively enhances brain AT2 receptor expression, and abolishes the cold-restraint stress-induced increase in tyrosine hydroxylase mRNA in the locus coeruleus of spontaneously hypertensive rats

Document Type

Journal Article

Publication Date

12-16-2008

Journal

Stress

Volume

11

Issue

6

DOI

10.1080/10253890801892040

Keywords

Angiotensin II receptors; Brain; Central sympathetic system; Locus coeruleus; Renin angiotensin system; Stress

Abstract

Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated orally for 14 days with the AT1 receptor antagonist candesartan before submission to 2 h of cold-restraint stress. In non-treated rats, stress decreased AT1 receptor binding in the median eminence and basolateral amygdala, increased AT2 receptor binding in the medial subnucleus of the inferior olive, decreased AT2 binding in the ventrolateral thalamic nucleus and increased tyrosine hydroxylase mRNA level in the locus coeruleus. In non-stressed rats, AT1 receptor blockade reduced AT1 receptor binding in all areas studied and enhanced AT2 receptor binding in the medial subnucleus of the inferior olive. Candesartan pretreatment produced a similar decrease in brain AT1 binding after stress, and prevented the stress-induced AT2 receptor binding decrease in the ventrolateral thalamic nucleus. In the locus coeruleus and adrenal medulla, AT1 blockade abolished the stress-induced increase in tyrosine hydroxylase mRNA level. Our results demonstrate that oral administration of candesartan effectively blocked brain AT1 receptors, selectively increased central AT2 receptor expression and prevented the stress-induced central stimulation of tyrosine hydroxylase transcription. The present results support a role of brain AT1 and AT2 receptors in the regulation of the stress response, and the hypothesis that AT1 receptor antagonists may be considered as potential therapeutic compounds in stress related disorders in addition to their anti-hypertensive properties. © 2008 Informa USA, Inc.

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