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 hypothalam ic-pituitary-adrenal (HPA) axis, including CRH cells in the hypothalam ic paraventricular nucleus (PVN), To determine whether brain AT(1) rec eptors are involved in the activation of the HPA axis and sympathetic system during stress, we studied the effects of acute immobilization s tress on plasma catecholamines, ACTH and corticosterone, and mRNA leve ls of CRH and CRH receptors (CRH-R) in the PVN in rats under central A T(1) receptor blockade by the selective antagonist, Losartan. While ba sal levels of epinephrine, norepinephrine and dopamine in plasma were unaffected 30 min after icy injection of Losartan (10 mu g), the incre ases 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 corticoster one levels were unaffected by icy Losartan treatment, Using in situ hy bridization studies, basal levels of CRH mRNA and CRH-R mRNA in the PV N were unchanged after icy Losartan, While Losartan had no effect on t he increases in CRH-R mRNA levels 2 or 3 h after 1 h immobilization, i t prevented the increases in CRH mRNA, The blunted plasma catecholamin e responses after central AT(1) receptor blockade indicate that endoge nous Ang II in the brain is required for sympathoadrenal activation du ring 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 r egulating CRH expression in the PVN.