Central AT1 receptor blockade with Losartan blunted the increases in plasma catecholamines during immobilization stress (P<0.05 for norepinephrine, P<0.01 for epinephrine and dopamine) in rats.
Does central AT1 receptor blockade with Losartan blunt sympathoadrenal and HPA axis activation during acute immobilization stress in rats?
Endogenous brain Angiotensin II is required for sympathoadrenal activation and regulates CRH expression in the PVN during immobilization stress in rats.
p-value: p=<0.05 for norepinephrine, <0.01 for epinephrine and dopamine
Angiotensin II (Ang II) type-1 (AT1) 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 AT1 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 AT1 receptor blockade by the selective antagonist, Losartan. While basal levels of epinephrine, norepinephrine and dopamine in plasma were unaffected 30 min after i.c.v. injection of Losartan (10 microg), 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 i.c.v. Losartan treatment. Using in situ hybridization studies, basal levels of CRH mRNA and CRH-R mRNA in the PVN were unchanged after i.c.v. 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 AT1 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.
Ježová et al. (Thu,) conducted a other in Acute immobilization stress. Losartan (intracerebroventricular injection) vs. Controls was evaluated on Plasma catecholamines (epinephrine, norepinephrine, dopamine) after 5 and 20 min stress (p=<0.05 for norepinephrine, <0.01 for epinephrine and dopamine). Central AT1 receptor blockade with Losartan blunted the increases in plasma catecholamines during immobilization stress (P<0.05 for norepinephrine, P<0.01 for epinephrine and dopamine) in rats.