Objectives: AT1A-receptors are expressed within the hypothalamo-pituitary-adrenal (HPA) axis and
seem to be important for its stress responsiveness. Secretion of corticotropin releasing
hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) is increased
through AT1-stimulation. In the present study we tested the hypothesis that a blockade
of angiotensin II effects attenuates HPA-axis reactivity in SHR which may belong to
the beneficial actions of AT1-antagonists.
Methods: SHR were either treated with candesartan (2mg/kg) or ramipril (1mg/kg) or mibefradil
(12mg/kg) for 5 weeks. In addition to baseline levels, CORT and ACTH responses to
injection of CRH (100µg/kg) were monitored over a period of 4h. Messenger RNA of CRH,
proopiomelanocortin (POMC), AT1A- AT1B- and AT2-receptors was quantified by real time
PCR.
Results: 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 (-39% and -42%). 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.
Conclusions: We show for the first time that antihypertensive treatment with inhibitors of angiotensin
II activity or generation 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 downregulation of hypothalamic
CRH expression have the potential to reduce HPA-axis activity during chronic AT1-blockade
or ACE inhibition.
