Angiotensin II inhibition reduces stress sensitivity of hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats

Walter Raasch*, Christian Wittmershaus, Andreas Dendorfer, Inga Voges, Friedrich Pahlke, Christoph Dodt, Peter Dominiak, Olaf Jöhren

*Corresponding author for this work
36 Citations (Scopus)


Angiotensin II type 1 (AT1) receptors are expressed within organs of the hypothalamo-pituitary-adrenal (HPA) axis and seem to be important for its stress responsiveness. Secretion of CRH, ACTH, and corticosterone (CORT) is increased by stimulation of AT1 receptors. In the present study, we tested whether a blockade of the angiotensin II system attenuates the HPA axis reactivity in spontaneously hypertensive rats. Spontaneously hypertensive rats were treated with candesartan (2 mg/kg), ramipril (1 mg/kg), or mibefradil (12 mg/kg) for 5 wk. In addition to baseline levels, CORT and ACTH responses to injection of CRH (100 μg/kg) were monitored over 4 h. mRNA of CRH, proopiomelanocortin, AT1A, AT1B, and AT2 receptors was quantified by real-time PCR. All treatments induced equivalent reductions of blood pressure and had no effect on baseline levels of CORT and ACTH. However, both candesartan and ramipril significantly reduced CRH-stimulated plasma levels of ACTH (-26 and -15%) and CORT (-36 and -18%) and lowered hypothalamic CRH mRNA (-25 and -29%). Mibefradil did not affect any of these parameters. Gene expression of AT1A, AT1B, and AT2 receptors within the HPA axis was not altered by any drug. We show for the first time that antihypertensive treatment by inhibition of AT 1 receptors or angiotensin-converting enzyme attenuates HPA axis reactivity independently of blood pressure reduction. This action is solely evident after CRH stimulation but not under baseline conditions. Both a reduced pituitary sensitivity to CRH and a down-regulation of hypothalamic CRH expression have the potential to reduce HPA axis activity during chronic AT 1 blockade or angiotensin-converting enzyme inhibition.

Original languageEnglish
Issue number7
Pages (from-to)3539-3546
Number of pages8
Publication statusPublished - 23.06.2006

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


Dive into the research topics of 'Angiotensin II inhibition reduces stress sensitivity of hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats'. Together they form a unique fingerprint.

Cite this