Angiotensin II AT1receptor blockade selectively enhances brain AT2receptor expression, and abolishes the cold-restraint stress-induced increase in tyrosine hydroxylase mRNA in the locus coeruleus of spontaneously hypertensive rats (original) (raw)

Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated orally for 14 days with the AT 1 receptor antagonist candesartan before submission to 2 h of cold-restraint stress. In non-treated rats, stress decreased AT 1 receptor binding in the median eminence and basolateral amygdala, increased AT 2 receptor binding in the medial subnucleus of the inferior olive, decreased AT 2 binding in the ventrolateral thalamic nucleus and increased tyrosine hydroxylase mRNA level in the locus coeruleus. In non-stressed rats, AT 1 receptor blockade reduced AT 1 receptor binding in all areas studied and enhanced AT 2 receptor binding in the medial subnucleus of the inferior olive. Candesartan pretreatment produced a similar decrease in brain AT 1 binding after stress, and prevented the stress-induced AT 2 receptor binding decrease in the ventrolateral thalamic nucleus. In the locus coeruleus and adrenal medulla, AT 1 blockade abolished the stress-induced increase in tyrosine hydroxylase mRNA level. Our results demonstrate that oral administration of candesartan effectively blocked brain AT 1 receptors, selectively increased central AT 2 receptor expression and prevented the stress-induced central stimulation of tyrosine hydroxylase transcription. The present results support a role of brain AT 1 and AT 2 receptors in the regulation of the stress response, and the hypothesis that AT 1 receptor antagonists may be considered as potential therapeutic compounds in stress related disorders in addition to their anti-hypertensive properties.