Brain angiotensin II modulates sympathoadrenal and hypothalamic pituitary adrenocortical activation during stress

Angiotensin II (Ang II) type-1 (AT(1)) receptors are present in areas of the brain controlling autonomic nervous activity and the hypothalamic-pituitary-adrenal (HPA) axis, including CRH cells in the hypothalamic paraventricular nucleus (PVN), To determine whether brain AT(1) receptors are involved in the activation of the HPA axis and sympathetic system during stress, we studied the effects of acute immobilization stress on plasma catecholamines, ACTH and corticosterone, and mRNA levels of CRH and CRH receptors (CRH-R) in the PVN in rats under central AT(1) receptor blockade by the selective antagonist, Losartan. While basal levels of epinephrine, norepinephrine and dopamine in plasma were unaffected 30 min after icy injection of Losartan (10 mu g), the increases after 5 and 20 min stress were blunted in Losartan treated rats (P < 0.05 for norepinephrine, and P < 0.01 for epinephrine and dopamine, vs controls), Basal or stress-stimulated plasma ACTH and corticosterone levels were unaffected by icy Losartan treatment, Using in situ hybridization studies, basal levels of CRH mRNA and CRH-R mRNA in the PVN were unchanged after icy Losartan, While Losartan had no effect on the increases in CRH-R mRNA levels 2 or 3 h after 1 h immobilization, it prevented the increases in CRH mRNA, The blunted plasma catecholamine responses after central AT(1) receptor blockade indicate that endogenous Ang II in the brain is required for sympathoadrenal activation during immobilization stress, While Ang II appears not to be involved in the acute secretory response of the HPA axis, it may play a role in regulating CRH expression in the PVN.